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36
Volume 3, Number 1 • January 2014 • www.gahmj.com
GLOBAL ADVANCES IN HEALTH AND MEDICINE
Review
REVIEW
Integrative Nanomedicine: Treating Cancer With Nanoscale
Natural Products
综合纳米医学：利用纳米级天然产物治疗癌症
Nanomedicina integral: Tratar el cáncer con productos naturales en nanoescala
Iris R. Bell, MD, PhD, United States; Barbara Sarter, PhD, APRN, FNP-C, United States; Mary Koithan, PhD, RN, United
States; Prasanta Banerji, FMIH, India; Pratip Banerji, MD(Hom), India; Shamini Jain, PhD, United States; John Ives,
PhD, United States
Author Affiliations
Department of Family
and Community
Medicine, The University
of Arizona College of
Medicine, Tucson (Dr
Bell); College of Nursing,
The University of
Arizona (Drs Bell and
Koithan); Hahn School
of Nursing and Health
Sciences, University of
San Diego, California,
and Bastyr University –
California (Dr Sarter);
PBH Research
Foundation, Kolkata,
India (Drs Banerji);
Samueli Institute,
Alexandria, Virginia
(Drs Jain and Ives).
Correspondence
Iris R. Bell, MD, PhD
ibell@email.arizona.edu
Citation
Global Adv Health Med.
2014;3(1):36-53. DOI:
10.7453/gahmj.2013.009
Key Words
Cancer treatment
protocols, Banerji
Protocols, complementary
and alternative
medicine, integrative
medicine, homeopathy,
nanomedicine, nanopar-
ticles, exosomes, nosodes,
hormesis, pulsed
drug dosing
Disclosure
The authors completed
the ICMJE Form for
Disclosure of Potential
Conflicts of Interest, and
Drs Kothan, Sarter,
Banerji, Jain, and Ives
disclosed no potential
conflicts of interest.
Dr Bell disclosed that she
is a consultant to
Standard Homeopathic/
Hylands Inc, a
United States–based
manufacturer of
homeopathic medicines.
Dr Bell also disclosed
funding to her
institution from the
National Institutes of
Health (NCCAM T32).
ABSTRACT
Finding safer and more eective treat-
ments for specific cancers remains a
significant challenge for integrative
clinicians and researchers worldwide.
One emerging strategy is the use of
nanostructured forms of drugs, vac-
cines, traditional animal venoms,
herbs, and nutraceutical agents in can-
cer treatment. The recent discovery of
nanoparticles in traditional homeo-
pathic medicines adds another point
of convergence between modern
nanomedicine and alternative inter-
ventional strategies. A way in which
homeopathic remedies could initiate
anticancer eects includes cell-to-cell
signaling actions of both exogenous
and endogenous (exosome) nanopar-
ticles. The result can be a cascade of
modulatory biological events with
antiproliferative and pro-apoptotic
eects. The Banerji Protocols reflect a
multigenerational clinical system
developed by homeopathic physi-
cians in India who have treated thou-
sands of patients with cancer. A num-
ber of homeopathic remedy sources
from the Banerji Protocols (eg, Calcarea
phosphorica; Carcinosin—tumor-
derived breast cancer tissue prepared
homeopathically) overlap those
already under study in nonhomeo-
pathic nanoparticle and nanovesicle
tumor exosome cancer vaccine
research. Past research on antineoplas-
tic eects of nano forms of botanical
extracts such as Phytolacca, Gelsemium,
Hydrastis, Thuja, and Ruta as well as on
homeopathic remedy potencies made
from the same types of source materi-
als suggests other important overlaps.
The replicated finding of silica, silicon,
and nano-silica release from agitation
of liquids in glassware adds a proven
nonspecific activator and amplifier of
immunological eects. Taken togeth-
er, the nanoparticulate research data
and the Banerji Protocols for homeo-
pathic remedies in cancer suggest a
way forward for generating advances
in cancer treatment with natural prod-
uct–derived nanomedicines.
摘要
对全世界的综合临床医生和研究人
员来说，针对特定癌症找到更安全
有效的治疗方法一直是一项严峻的
挑战。 一项新兴战略是采用纳米结
构形式的药物、疫苗、传统动物毒
液、草药和保健食品剂进行癌症治
疗。 针对传统顺势疗法药物纳米颗
粒 (NP) 的一项近期发现结果，在现
代纳米医学与替代性干预战略之间
又新发现了一个共同点。 顺势疗法
启动抗癌作用的方式包括外源性和
内源性（外泌体）纳米颗粒的细胞
间信号活动。 这一结果可能是调节
生物活动与抗增殖作用和细胞凋亡
作用之间产生的级联反应。 Banerji
实验方案反映了印度顺势疗法医生
在治疗了数以千计的癌症患者之后
制定的多世代临床系统。 许多源自
于 Banerji 实验方案的顺势疗法（
如，磷酸钙；癌素—采用顺势疗法
从肿瘤中衍生制备的乳腺癌组织）
与非顺势疗法纳米颗粒和纳米囊泡
肿瘤外泌体癌症疫苗研究中所研究
的疗法存在共同之处。 针对纳米形
式的植物提取物（如，商陆属、断
肠草属、白毛莨属、金钟柏属和芸
香属）抗肿瘤作用以及同类原材料
的顺势疗法潜能进行的过往研究表
明，二者之间还存在其他重要的共
同之处。 研究人员从搅动玻璃器皿
中液体所释放出的产物中一再发现
二氧化硅、硅和纳米硅，为免疫学
反应又新找到了一个经证实的非特
异性催化剂和放大剂。 综合起来，
对癌症的顺势疗法来说，纳米颗粒
研究数据和 Banerji 实验方案表
明，采用源自于天然产物的纳米医
药治疗癌症是推动癌症治疗取得进
展的一种方式。
SINOPSIS
Encontrar tratamientos más seguros
y más eficaces para cánceres específi-
cos sigue siendo un desafío significa-
tivo para los médicos integrales e
investigadores en todo el mundo. Una
estrategia emergente es el uso de for-
mas nanoestructuradas de fármacos,
vacunas, venenos animales tradicio-
nales, hierbas y agentes nutracéuticos
en el tratamiento del cáncer. El reci-
ente descubrimiento de las
nanopartículas en medicinas homeo-
páticas tradicionales aporta otro
punto de convergencia entre la nano-
medicina moderna y las estrategias
intervencionistas alternativas. Una
manera en la que los remedios
homeopáticos podrían iniciar efectos
anticancerígenos incluye acciones de
señalización entre células de nano-
partículas exógenas y endógenas
(exosoma). El resultado puede ser una
cascada de acontecimientos biológi-
cos moduladores con efectos antipro-
liferativos y proapoptóticos. Los pro-
tocolos de Banerji reflejan un sistema
clínico multigeneracional desarrolla-
do por médicos homeopáticos en la
India que han tratado a millares de
pacientes con cáncer. Un número de
fuentes de remedios homeopáticos de
los protocolos de Banerji (p. ej., cal-
cárea fosfórica; carcinosina, tejido
derivado del tumor de cáncer de
mama preparado homeo pática-
mente) se solapan con aquellos estu-
diados en la investigación de la vacu-
na para el cáncer de exosomas tumo-
rales nanovesiculares y nano partí-
culas no homeopáticas). Anteriores
www.gahmj.com • January 2014 • Volume 3, Number 1
37
Review
INTEGRATIVE NANOMEDICINE CANCER TREATMENT
INTRODUCTION
The purpose of this article is to provide an overview
of natural product nanomedicine for cancer treatment
as a foundation for understanding the more than
200-years-old complementary and alternative medicine
(CAM) system of homeopathy. Historically, various
homeopaths have reported successful treatment of
patients with cancers using natural product–derived
medicines.1-4 Main topics addressed here are (1) the
rationale for using nanoscale forms of natural products
in cancer treatment; (2) the evidence for homeopathic
medicines as nanoparticle-based natural products; (3)
data on studies of homeopathy in cancer treatment; and
(4) the Banerji Protocols as a promising clinical approach
to cancer using homeopathic remedies, with parallels to
research on modern manufactured nanoparticles.
Finding safer and more effective treatments for
specific cancers remains a significant challenge for
integrative clinicians and researchers worldwide. One
emerging strategy is the use of nanostructured forms of
drugs, vaccines, herbs, and nutraceutical agents in can-
cer treatment.5-10 At the nanoscale range, the source
material is typically in the ultrafine particle size range
of 1 to 100 nanometers (nm) along at least one side,
although some consider nanoforms to include particle
sizes up to 1000 nanometers (see Table 1 for definitions
of common terms in nanoparticle manufacturing).
Poorly soluble drugs or natural source materials
pose practical challenges for administration and effec-
tive treatment. In such situations, preparing a medicine
or natural product in nano form confers multiple advan-
tages over conventional bulk form drugs.15,16 These
Table 1 Glossary of Nanoparticle Terms11
Term Definition
Nanoparticle Very small particle made from a specific source material and measuring between 1 and 100 nm in length along at least
one side (1 nanometer=10-9 m).
The very smallest nanoparticles are called quantum dots (size range 1-10 nm long on a side) because of the
large percentage of atoms of material close to the surface of the particle and the atom-like quantum mechanical
properties that can manifest at that size.
Top-down
manufacturing
One of multiple procedures for breaking smaller and smaller particles off an initially larger-scale bulk form material to
generate nanoparticles.
Examples include mechanical grinding and milling, photolithography, laser beam processing.
Bottom-up
manufacturing
One of multiple procedures for building up or assembling a nanostructure or nano-network from small, nanoscale
building blocks. Process usually relies on a template.
Interactions between the building blocks to assemble the nanostructure can include electrostatic forces, hydrogen
bonds, and other weak forces.
Examples include organic synthesis by plant or fungal extracts, self assembly on DNA12 or protein templates,13 and
colloidal aggregation. Silica nanoparticles can form durable biocomposites using living cells as 3-dimensional templates.14
Capping agent A substance added to a nanoparticle manufacturing process that stabilizes the nanoparticles and prevents them from
agglomerating together once formed.
Examples range from toxic polymer chemicals to natural agents such as ascorbic acid, lactose, or honey.
Agglomeration Clustering of nanoparticles together into larger structures. This process changes size and surface energies and thus can
alter the properties.
Ostwald ripening A spontaneous thermodynamic process of liquid sols allowed to age. Smaller nanoparticles condense or redeposit onto
larger particles. Energetic instability of surface components of the smaller particles contributes to the process.
Brownian motion Irregular motion of nanoparticles suspended in a liquid solution or gas. Caused by interaction of the particles with the
medium or solvent.
Adsorption The accumulation of solutes, liquids, or gases onto the surface of a nanoparticle. For nanoparticles, adsorption is related
in part to the high surface charge and energy.
Self-assembly The capacity of a system to generate an ordered or organized structure from initially unordered building blocks
(see bottom-up manufacturing).
Dopant An impurity or substance added in very small quantity to a pure semiconductor material to modify its conductive
properties.
Arsenic, boron, or phosphorus are common dopants for different semiconductor materials, including silicon.
investigaciones sobre los efectos anti-
neoplásicos de nanoformas de extrac-
tos botánicos como la Phytolacca,
Gelsemium, Hydrastis, Thuja y Ruta
así como sobre la potencia de los
remedios homeopáticos derivados de
las mismas clases de materiales de
origen sugieren otras coincidencias
importantes. El descubrimiento repli-
cado de la liberación de silicio, silico-
na y nanosilicio de la agitación de
líquidos en cristal añade un activador
inespecífico probado y un amplifica-
dor de los efectos inmunológicos. En
conjunto, los datos de la investigación
de nanopartículas y los protocolos de
Banerji de remedios homeopáticos en
el cáncer sugieren un camino a seguir
para avanzar en el tratamiento del
cáncer con nanomedicinas derivadas
de productos naturales.
38
Volume 3, Number 1 • January 2014 • www.gahmj.com
GLOBAL ADVANCES IN HEALTH AND MEDICINE
Review
advantages include enhanced bioavailability, adsorptive
capacity, and intracellular accessibility.17,18 The smaller
nanoparticles can cross cell membranes readily, includ-
ing thosein the skin and even the blood-brain barrier.
Biological targeting with modern nanomedicines is
increasingly precise, including ability to foster specific
uptake into malignant cells, stop proliferation, and
increase apoptosis with less damage to healthy cells.19-21
Nanoparticles also can acquire atom-like properties
and high surface charge because of their small sizes and
large surface area to volume ratios. The altered nanoparti-
cle properties include increased chemical and biological
reactivity, electromagnetic, optical, thermal, and quan-
tum effects.22 In turn, the unique properties of nanomedi-
cines typically reduce required doses by orders of magni-
tude and improve side effect profiles.18,23-26 Minor varia-
tions in surface properties can enhance nanoparticle
uptake, especially into cancer cells, eg, conjugation with
the disaccharide sugar lactose.27,28 Surface adsorption of
sugars also may enhance immune system responsivity to
antigen delivered in vaccines by nanocarriers such as cal-
cium phosphate.29
Nanoparticles under study as diagnostic tools,
drug and vaccine delivery vehicles, and biological
agents in their own right include
•various metals (eg, silver, gold);
•metal salts (eg, calcium phosphate, magnesium
phosphate)30-32;
•Semiconductors (eg, silicon and its dioxide silica)33-35;
•lipid- or polysaccharide-based carriers (eg, Poly(lactide-
co-glycolic acid) [PLGA] or chitosan)36,37; and
•exosomes.38
Exosomes are nanosized endogenous vesicles from
endosomes released by a variety of cells containing
proteins, siRNA, and lipids with capabilities for sys-
temic biological signaling.6,39-43 Certain exogenous
nanoparticles can also trigger exosome release and a
cascade of systemic stress-related or pro-apoptotic sig-
naling in the immune and inflammatory pathways as
well.42-46 In the immune system, mature dendritic cells
pulsed with exosomes can stimulate antitumor activi-
ty.47 Exosomes derived from malignant tumor cells are
also used as experimental cancer treatment vaccines.6
NANOSCALE FORMS OF NATURAL PRODUCTS FOR
CANCER TREATMENT
One limitation in moving from bench to bedside
with nanoparticle diagnostic and therapeutic approach-
es in mainstream medicine has been concern about the
potential toxicity of nanomaterials. Some nanoparti-
cles are especially likely to accumulate in bodily tis-
sues. For instance, unmodified silver or copper nanopar-
ticles can exhibit toxicity risks.48 Because of their high
adsorptive ability and large surface areas, nanoparticles
can also retain trace amounts of any toxic solvents,
polymer chemicals, botanical agents, or trace metal
dopants used in manufacturing.49 Surface modifica-
tions of nanoparticles can create agents with very dif-
ferent chemical and/or biological properties from the
“same” nanoparticles with unmodified surfaces.28,50,51
An offshoot of this concern has been a shift
toward “green manufacturing” methods. For instance,
nanotechnologists use natural products such as botan-
ical or herbal agents or other types of living organisms
to biosynthesize gold or silver nanoparticles.9,52,53
Then trace amounts of the more benign plant material
remain adsorbed to the outer nanoparticle surfaces,
thereby modifying the nanoparticle sizes and biologi-
cal effects.9 Manufacturing procedures that attach a
benign sugar such as lactose to the surfaces of silver
nanoparticles can also markedly enhance nanoparticle
uptake into malignant, but not healthy cells.28 Plant
extracts, DNA, and proteins also guide bottom-up
manufacturing via self-assembly of silica precursors
into crystalline silica nanostructures54,55 that can
resist drying in some preparations.56
In addition, researchers make nano-encapsula-
tions of certain natural, less soluble products from
herbs or nutraceuticals. Such nanoforms can overcome
gastrointestinal uptake and cellular accessibility prob-
lems of their respective bulk forms in vivo.16 Thus,
nanoparticle forms of antioxidants with antiinflamma-
tory and antiproliferative properties have markedly
enhanced their potential utility for cancer therapy
compared with their bulk forms. Examples include
nano-forms of curcumin,37,57-60 quercetin,5,61,62 and
coenzyme Q10.63 PLGA nano-encapsulated herbal
extracts of Gelsemium sempervirens also acquire
improved anticancer effects.64,65 Overall, nanoscale
forms of natural products add a clinically valuable
method for delivering less toxic or nontoxic treatments
to people with cancers in which the currently available
mainstream approaches are less effective, prone to drug
resistance, and/or highly toxic. Given acceptable treat-
ment efficacy, lower toxicity can translate into better
patient outcomes.
HOMEOPATHIC REMEDIES AS NANOMEDICINES
Homeopathy is a more than 200-years-old system
of alternative medicine developed by the German physi-
cian-chemist Samuel Hahnemann, MD. This type of
healthcare is used widely around the world. Homeopathy
is especially popular in India, the United Kingdom,
Germany, France, Belgium, and several Latin American
nations. Homeopathic medicines derive from natural
mineral, plant, and animal sources, sometimes includ-
ing diseased tissues (ie, nosodes such as Carcinosin,
homeopathically prepared breast cancer tumor).66
Unlike in conventional healthcare, the classical
homeopathic diagnosis (ie, remedy selection) depends
on describing the total clinical pattern of biopsychoso-
cial symptoms. Homeopathically relevant symptoms
include adaptive behaviors of the individual person as
an indivisible complex system. Classical remedy pre-
scriptions then involve matching the patient’s com-
plete picture with the previously documented ability of
www.gahmj.com • January 2014 • Volume 3, Number 1
39
Review
INTEGRATIVE NANOMEDICINE CANCER TREATMENT
a specific single remedy to cause the same pattern in
healthy persons. Thus, by definition, homeopathic
treatment relies on both (1) individual salience and (2)
state dependency in the host to elicit beneficial rather
than adverse effects. Remedy dosing typically involves
pulsed or intermittent administration at lower doses
and lower frequency than used in conventional bulk
drug treatment.66
A recent development in integrative medicine
research is the discovery of persistent nanoparticles of
source materials (eg, metals, plants) in homeopathic
medicines, sometimes referred to as “remedies” (Figure
1).67-69 Different homeopathic plant remedy tinctures
can also biosynthesize silver nanoparticles, with the
resultant nanoparticles. The homeopathic plant-modi-
fied silver nanoparticles vary slightly in size and demon-
strate somewhat different biological effects against a
melanoma cancer cell line in vitro as a function of the
plant source material.9 In the latter study, the plant-
made variants of silver nanoparticles exhibited antican-
cer effects involving both cell cycle arrest and apoptosis.
Only recently, some homeopaths and nanoscien-
tists recognized the extensive overlaps between green
manufacturing of modern nanoparticles and tradition-
al homeopathic manufacturing methods.9,68,70
Homeopathic manufacturing standards derive from
the empirical techniques originally developed by
Hahnemann in the 19th century.71 The essential pro-
cess of making homeopathic medicines includes72
•natural remedy source materials (plant, mineral,
animal, disease tissue sources);
•preparation of ethanolic extracts or tinctures;
•extensive grinding of source materials in lactose;
and
•serial dilutions and repeated succussions (agitation)
in ethanol-water diluent within glass containers.
Homeopathic manufacturing procedures involve
preparation of an ethanol-based extract (plants, disease
tissue) and/or trituration (grinding or milling) in lactose
over a long period of time for insoluble materials. The
ground or milled remedy in lactose is then serially
diluted, first in dry lactose for the first few steps and then
in ethanol-water diluent in glass containers over multi-
ple subsequent steps. The dilution ratios are typically
1/10 (X or D potencies) or 1/100 (C potencies), followed
by vigorous agitation of the solution. Manual manufac-
Figure 1 Bright field transmission electron microscope (TEM) images of nanoparticles and aggregates in homeopathically prepared gold
(Aurum metallicum) at 30C (e) and 200C (f) potencies from Indian manufacturer SBL (originally Sharda Boiron Laboratories, Ltd, Delhi,
India) and 30C (g) and 200C (h) potencies from the different Indian manufacturer WSI (Schwabe International GmbH, Germany, per Dr
Willmar Schwabe India Pvt Ltd, Noida, Uttar Pradesh, India). Bulk form remedy source material was presumably diluted out of solution
beyond the 12C potency. Reprinted with permission from Chikramane et al, 2010.68
40
Volume 3, Number 1 • January 2014 • www.gahmj.com
GLOBAL ADVANCES IN HEALTH AND MEDICINE
Review
turing methods involve 10-100 vigorous succussions per
dilution step (agitation in solution by pounding the
glass container against a hard surface).64
From the dilution process per se, skeptics have
long assumed that homeopathic medicines could not
plausibly contain any residual molecules of the source
material, at potencies with bulk dilutions past 24X or
12C (ie, diluted past the cut-off for Avogadro’s number
of molecules). They have generally overlooked the
potential role of the other steps in the manufacturing
process for generating bioactive agents. Debates over
the validity of homeopathy center on this primary
dilution argument.73-77
However, new data indicate that while the specif-
ic manufacturing methods for classically prepared
remedies probably remove the bulk source materials
early in the process of serial dilutions, they leave a
layer of detectable source nanoparticles across all dilu-
tions. The data include remedy potencies diluted past
Avogadro’s number for bulk materials (Figure 2).67
Chikramane et al showed heterogenous accumulation
of nanoparticles in a top layer as a result of the creation
and movement in solution of bubbles and nanobub-
bles during succussions. The latter group also pro-
posed that the lactose can serve as a capping agent for
nanoparticle growth during trituration67 as well as a
vehicle for delivering nanoparticles.78,79
The specific alcohol itself (ie, ethanol) and its con-
centration also can modify the properties of nanopar-
ticles made in liquid solutions.80-82 Agitating a solu-
tion of nanoparticles can also help disperse any spon-
taneous agglomerations of larger clusters into smaller
particles.83,84 Thus, nanoparticles of the source mate-
rial are found from the lowest to the highest homeo-
pathic potencies across all dilutions. Dilution appears
to remove bulk forms but not nanoscale forms of
source material.
Furthermore, the succussion process generates read-
ily measurable amounts of silicon, silica (silicon dioxide),
and its precursors from the glass walls of the contain-
er.64,69,85,86 Studies on different glassware containing
succussed homeopathic remedies, agitated non-homeo-
pathic liquid solutions, and succussed control solutions
all demonstrate the variable release of biologically active
silica and related chemicals into solution.69,85,87
Numerous studies show that silicon and silica nanopar-
ticles and crystals can adsorb or attach to source nanopar-
ticles as drug delivery vehicles,87,88 and/or nonspecifical-
ly amplify their biological effects, especially those in the
immune system.45,88,90 Certain forms of porous nanosili-
con possess relatively low toxicity and biodegradability
in medical applications, including sensitizing the photo-
dynamic killing of cancer cells.91 Very small silicon
nanoparticles (quantum dots), depending on their dop-
ant materials, can also generate unique optical effects
and transport electric charges: eg, in solar cells.92,93
1 000 000
100 000
10 000
1000
100
10
<1
0 1c 2c 3c 4c 5c 6c 7c 8c 9c 10c 11c 12c 13c 14c 15c
1021041061081010 1012 1014 1016 1018 1020 1022 1024 1026 1030
1028
Serial Centesimal Dilutions in 90%v/v Ethanol
Dilution Factors
Concentration of AuNPs (ng/ml)
AuNPs + Lactose
TL
ML
Bulk
TL 15C-0.103 ng/mL
(103pg/mL)
Figure 2 Estimation of gold nanoparticle (AuNPs) concentrations in top layer (TL) and middle layer (ML) after dilution and succussion
of commercial AuNPs using classic homeopathic lactose trituration, ethanol-water dilution, and succussion procedures. Beyond the 6C
potency, 99% of the AuNPs are transferred to the next dilution. The original authors indicate that these findings result from a bubble-
induced froth flotation process of nanoparticles forming a monolayer at the air-liquid interface. Reprinted with permission from
Chikramane et al, 2012.67
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INTEGRATIVE NANOMEDICINE CANCER TREATMENT
Notably, as with silver, plant tinctures can also
biosynthesize nanocrystals of silica from its precur-
sors.55 Therefore, in addition to the remedy source
nanoparticles, the nanosilica and silica crystals from
agitation of liquid solutions within glassware likely
provide an additional remedy-modified delivery vehi-
cle and nonspecific amplifier of biological effects relat-
ed to the specific remedy source.70,94 The documented
variability in release of silicon, silica, and its precursors
from different types of glassware87 could contribute to
the well-known variability reported in both basic sci-
ence and clinical trial studies of homeopathically-pre-
pared medicines.95,96 From a nanotechnology perspec-
tive,15,82,84,97,98 methodological variations in homeo-
pathic source materials, grinding procedures, dilutions,
succussion procedures, pH, temperature, and ethanol
concentrations during remedy preparation would also
affect the sizes, shapes, amounts, and properties of the
final homeopathic medicines. Even aging during stor-
age can significantly change the properties of both
nanoparticles99-101 and homeopathic remedies.102
What would the presence of nanosilica add to
natural product cancer treatment? Several nonhomeo-
pathic studies of the effects of a traditional Middle
Eastern animal venom–derived treatment on cancer
cells begin to answer that question. The addition of
modern manufactured silica nanoparticles to a snake
venom–derived medicine significantly enhanced the
apoptotic and growth arrest effects of the treatment on
breast cancer cells (Figure 3).103 The same type of com-
bination treatment (snake venom with silica nanopar-
ticles) also improved anticancer effects against malig-
nant myeloma cells104 and human prostate cancer
cells.105 Like certain types of nanoparticles,106-108 some
homeopathic remedies with antineoplastic properties
exhibit the ability to attack cancer cells while leaving
healthy cells intact.109,110
Most nanomedicine applications of natural
products are still in developmental or early clinical
trial phases of study.5,111 However, with the discov-
ery of nanoparticles in homeopathic remedies, both
homeopathic manufacturers and modern nanomed-
icine practice stand to learn from each other. The
overall goal would be to improve research and clini-
cal care of people with cancer using less toxic natu-
rally-based interventions.
What nanoscience brings to homeopathy is mod-
ern technological methods. Nanomedicine research
insights into nanoparticle characterization and how
nanoparticles interact with living systems can help
homeopathic investigators design better products
and improve reproducibility from study to study.68,112-
114 On the other hand, homeopaths possess over two
centuries of practical clinical experience and texts on
using their naturally-sourced nanoparticles safely to
treat patients. Modern nanomedicine could benefit
from these real-world homeopathic experiences with
nanoparticle-based clinical practice. Multiple studies
on cancer cell cultures and animals indicate that both
modern nanomedicines and homeopathic remedies
have beneficial effects in vitro and in animals toward
promoting apoptosis and modulating biological sig-
naling pathways to limit cancer cell growth.115-117
Accelerating targeted research and identifying opti-
mal treatments for people with cancer could result.
Table 2 lists relevant studies that suggest paral-
lels between some mainstream natural product nano-
medicine agents and homeopathic remedy effects.
The evidence to date suggests that nanoparticle forms
of a number of natural products can treat cancer. For
instance, nanoparticles from certain mineral salts
such as calcium phosphate,31,118 the metalloid arse-
nic,135 a variety of specific plant extracts (concen-
trated mother tinctures),9 animal venom toxin treat-
ments,103-105,136 and exosomes (endogenous nanopar-
ticles released by bodily cells) from cancerous tissue
or dendritic cells of the immune system6 can all exert
antiproliferative and pro-apoptotic effects on specific
cancer cell lines in in vitro. Several plant nanoparti-
cle studies used homeopathic mother tinctures to
manufacture the nanoparticles.9 Moreover, studies of
specific homeopathic remedies prepared in potencies
ranging from 3X to 1000C (1M) made from mineral
salts (calcium phosphate), certain plants, and cancer-
ous tissue and used in clinical treatment of people
with cancer also reveal similar effects.1,2,109,110
As noted above, homeopathy potentially brings to
integrative clinical nanomedicine treatment for cancer a
well-described practice theory and more than 200 years
of clinical experience. For homeopathy, the data indicate
high patient satisfaction, very low toxicity, no drug-drug
80
60
40
20
0
% Apoptotic Cells
MDA-MB-231 MCF-7 MCF-10
Control
NP
WEV
WEV+NP
*
*
#*
#*
Figure 3 Silica nanoparticles amplify apoptotic effects of biologi-
cally active natural agent. Data from five different experiments
are expressed as the mean percentage of apoptotic cells ± SEM
for the control (open bars), NP-treated (gray bars), WEV-treated
(closed black bars), and WEV+NP–treated (hatched bars). *P < .05,
WEV-treated vs NP; #P < .05, WEV+NP-treated vs NP; +P < .05,
WEV+NP-treated vs WEV-treated cells. WEV = venom of Walterin-
nesia aegyptia snake; NP = silica nanoparticles. MDA-MB-231 and
MCF-7 are human breast cancer cells; MCF-10 are normal breast
epithelial cells. Reprinted with permission from publisher S. Karger
AG, Basel, from reference.103
42
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GLOBAL ADVANCES IN HEALTH AND MEDICINE
Review
or drug-herb interactions, and low side effect rates.95,96
Allergic reactions at low potencies may be a minor
risk,137,138 though the rates appear to be extremely low,
serious events are rare, and relatedness to the remedies
per se uncertain.96,139,140 In one sense, homeopaths in
clinical practice may be many years ahead of conven-
tional physicians in applied understanding of how and
when to use nanoparticles of natural products for safe
and effective clinical treatment.
HOMEOPATHIC REMEDIES IN CANCER CARE
Although there is a growing research literature on
the effects of homeopathic remedies on cancer in cell
culture and animal studies, there are very few clinical
trials of homeopathy in cancer patients. Most reports in
the literature involve case reports.2,141 A long-articulated
concern of mainstream healthcare providers has been
the presumption that homeopathy and other forms of
complementary and alternative interventions are
Table 2 Parallels Between Effects of Modern Nanoparticles and Homeopathically-prepared Medicines on Cancer Cells
Mainstream
Nanoparticle Studies
Cancer Cell Types
Affected by Nanoparticles
Homeopathically-prepared
Medicines
Cancer Cell Types Affected
by Homeopathy
Calcium Phosphate
Nanoparticles (80 nm size
had greater effects than 20
nm size)31
Hydroxyapatite
nanoparticles118,119-122
MG-63 osteosarcoma cells
Brain cancer (glioma); decrease
toxicity of chemotherapy drugs118
Leukemia P388 tissue120
Liver tissue
Gastric cancer
Calcarea phosphorica 3X109
(low potency: bulk and
nanoparticles both likely
present)
Osteosarcoma (clinical case
reports)
Brain cancer (glioma)
Tumor cell-derived
exosomes6,38-41
Leukemia
Lymphoma
Colon melanoma
Lung cancer
Mesothelioma
Skin melanoma
Pancreatic cancer cells
Carcinosin 200C110 (breast cancer
tissue nosode remedy)
Breast cancer cells
Ruta Graveolens 6C109
Ruta Graveolens 200C123,124
Thuja 30C and 200C125
Brain cancer (glioma)
Ehrlich Ascites Carcinoma and
Dalton’s Lymphoma Ascites
Liver tumor
Hydrastis 200C124
Hydrastis 1M (1000C)126
Ehrlich Ascites Carcinoma and
Dalton’s Lymphoma Ascites
B16F-10 Melanoma
Lycopodium 30C127
Lycopodium 200C128
Lycopodium 1M126
Liver cancer
Liver cancer
B16F-10 Melanoma
Gelsemium sempervirens
extract encapsulated with
PLGA nanoparticles65,129
Skin cancer line A375
Phytolacca decandra extract
encapsulated with PLGA
nanoparticles130
Lung adenocarcinoma Phytolacca decandra 200C110
Conium maculatum 3C110
Thuja occidentalis 30C110
MCF-7 and MDA-MB-231 breast
cancer cells
Chelidonium 30C and 200C131 Liver tumor
Phytolacca decandra,
Gelsemium sempervirens,
Hydrastis canadensis,
Thuja occidentalis extracts
biosynthesize silver
nanoparticles9
A375 skin melanoma cells
Secale 30C115 Skin papilloma
Polygala senega extract
encapsulated with PLGA
nanoparticles132
A549 lung cancer cells
Homeopathic combination
medication Canova (originally,
Aconitum napellus D11,
Arsenicum album D19, Bryonia
alba D18, Lachesis mutus D18,
Thuja occidentalis D19)133,134
Sarcoma 180
PLGA is a copolymer poly(lactic-co-glycolic acid), a widely-used nanoparticle form.
Botanical extracts are homeopathic mother tinctures in ethanolic solutions (concentrated bulk form materials).
Homeopathic potencies are serially diluted and succussed in accord with standard manufacturing methods. “D” potencies are equivalent to “X” decimal
potencies (serial dilution factor of 1 part source to 9 parts diluent or solvent or a ratio of 1/10). Each dilution step is followed by 10 or more succussions.
www.gahmj.com • January 2014 • Volume 3, Number 1
43
Review
INTEGRATIVE NANOMEDICINE CANCER TREATMENT
ineffective and could dangerously cause patients to
delay more effective conventional treatments (ie, con-
ventional chemotherapy, radiation therapy, surgery) of
life-threatening serious diseases such as cancer. Partly
as a result, homeopathic cancer research in Western
countries has largely confined itself to preclinical stud-
ies and evaluations of adjunctive treatments of the side
effects of conventional cancer treatments.142
In that context, one small double-blind placebo-
controlled trial showed significant benefits of a com-
plex combination homeopathic remedy Traumeel
(Heel, GmbH, Baden-Baden, Germany) for treating che-
motherapy-induced stomatitis in children undergoing
stem cell transplantation.143 A positive phase III ran-
domized clinical trial on 254 patients demonstrated
that homeopathic Calendula was significantly more
effective in preventing acute dermatitis during adju-
vant radiation therapy than a standard of care topical
agent.144 An observational study of individualized
homeopathy for radiation-induced itching in breast
cancer patients suggested that homeopaths identified
several other specific beneficial remedies for 21 out of
25 individuals.145
Other trials of specific remedies for specific con-
ventional cancer treatment side effects were negative
or mixed, suggesting either lack of benefit or homeo-
pathic and researcher limitations in choosing and/or
managing the correct remedies.142,146,147 The emergent
conclusion from considering both the general and can-
cer-related homeopathic research literatures is that, as
in conventional medicine, proper selection of the cor-
rect medicine for a given patient with a given clinical
condition makes a difference as to whether or not
homeopathic treatments are likely to work. The hetero-
geneity of patients, diagnoses, and remedy and potency
effects make it essential to begin with tapping exten-
sive clinical experience in designing research on
homeopathic remedies and cancer that has reasonable
face, model, and external validity.148
THE BANERJI PROTOCOLS: USING HOMEOPATHIC
REMEDIES TO TREAT CANCER
What is the experience of homeopaths in more
comprehensive treatment of patients with cancer?
India is a country with perhaps the most extensive his-
tory in this regard. In contrast with countries such as
the United States or United Kingdom, India maintains
more than 100 teaching institutions on homeopathy,
many associated with universities, including 4- or
5-year homeopathic medical schools. These facilities
include hospitals and homeopathic pharmacies, and all
government hospitals include homeopathic treatment.
Private practitioners often develop large clinics staffed
by multiple homeopathic physicians, treating thou-
sands of patients for all types of acute and chronic con-
ditions, including cancers. Several different homeo-
pathic approaches to treating all types of cancers have
evolved in this context.1,3,4
Only one such approach, the Banerji Protocols,
however, has submitted its clinical cases to successful
review in the Best Case Series Program of the National
Cancer Institute (NCI) in the United States.2,149 After
this review, NCI’s Office of Cancer Complementary and
Alternative Medicine prioritized additional research on
this treatment approach. Nonetheless, historical skepti-
cism about the nature and plausibility of homeopathic
remedies as biologically active agents previously limit-
ed interest in pursuing research on homeopathy in the
United States. The emerging data on the natural nano-
medicine nature of homeopathic remedies is beginning
to shift the discussion.
The Banerji Protocols are based on the cumulative
experience of three generations of homeopaths treat-
ing thousands of patients.1 It is an empiric treatment
system developed through careful analysis of observed
trends in patient-medicine interaction. These exten-
sive practical experiences ultimately led to standard-
ized disease or symptom-specific protocols for pre-
scribing homeopathic medicines. This standardization
of treatment has made it possible to apply rigorous
scientific methods to test its efficacy. Collaborators
from around the world have recently organized a con-
sortium to coordinate their various efforts to advance
the clinical and laboratory research on the Banerji
Protocols. Because of their reputation for effective
clinical treatment of many cancers that generally have
a poor prognosis, we seek to apply the principles of
nanoparticle behavior to the particular approach used
in these protocols.
Given that an average of 120 to 200 cancer cases a
day are treated at the PBH Research Foundation,
Kolkata, India, there is a fertile ground for further inves-
tigation of this treatment method. A majority of the
cancer cases treated at this facility are not treated with
any other therapy, although there is no explicit require-
ment that this be so. In fact, most of the thousands of
consultations that are provided to patients from other
countries are from patients who have already had or are
currently undergoing conventional Western treat-
ment. Concomitant or previous conventional cancer
treatment is not considered to be a contraindication to
the Banerji Protocols.
However, a recent case review conducted by one of
our authors (Sarter, unpublished data) revealed that for
all categories of brain neoplasms, the cases that were
treated with the Banerji Protocols alone (1) fared sub-
stantially better in terms of fewer adverse events than
those that were combined with conventional Western
treatment and (2) had median survival estimated by the
Kaplan Meier method comparable to those reported in
the Surveillance, Epidemiology, and End Results data-
base of the NCI (http://seer.cancer.gov/). This provides
support for the premise that homeopathic nanomedi-
cines stimulate a robust host-dependent immune
response from healthy cells that is typically impaired
by chemotherapy and radiation therapy.150
Other distinguishing characteristics of the Banerji
Protocol are (1) its combination of multiple medicines
44
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GLOBAL ADVANCES IN HEALTH AND MEDICINE
Review
into a treatment regimen, (2) repeated daily or weekly
dosing over many months, and (3) the actual mixing
together of some homeopathic medicines into stan-
dardized combination remedies. All of these are in
contradiction to traditional classical homeopathy’s
principles of treatment.66,151 The protocols for the dif-
ferent types of cancer are mostly customized accord-
ing to the specific location, organ and tissue type, and
the specific medicines, in their specific dilutions and
dosage patterns, have been standardized after genera-
tions of experience.1
Thus, it appears plausible that in addition to a
general stimulation of the immune system, there is
also a tumor-specific effect in which tumor cells are
preferentially killed but normal cells preserved.105,106
As noted above, nanoparticles are capable of these
types of differential effects on diseased vs healthy
cells.31,106,108 One hypothesis for this phenomenon is
the greater “leakiness” of blood vessels in tumors. As
a result, malignant cells may permit greater uptake of
nanomedicines as opposed to healthy cells.16,152
Studies conducted to date in which specific
tumor cell lines are treated with the Banerji Protocol
medicines have supported this hypothesis. One
report on the Banerji protocols109 described 15
patients diagnosed with documented intracranial
tumors who were treated exclusively with the homeo-
pathic remedies Ruta graveolens 6C and Calcarea phos-
phorica 3X without additional chemotherapy or radia-
tion. Of these 15 patients, six of the seven who had
glioma showed complete regression of the tumors. In
this study, we also reported that these medicines
stimulated induction of survival-signaling pathways
in normal lymphocytes and induction of death-sig-
naling pathways in brain cancer cells. Cancer cell
death was initiated by telomere erosion and com-
pleted through mitotic catastrophe events.109 Bulk
herbal extract forms of Ruta graveolens have also dem-
onstrated the ability to exert antitumor effects, but
with some caveats on possible risks from prolonged
use at high doses.123,153-156 The ability to use low
doses of Ruta in nanoparticle form might help reduce
such risks.123,126,157
More recently, Frenkel et al reported a study of
four homeopathic remedies from the Banerji protocols
for treating breast cancer.110 The remedies were tested
against two human breast adenocarcinoma cell lines
(MCF-7 and MDA-MB-231) and a cell line derived from
immortalized normal human mammary epithelial
cells. The homeopathic medicines exerted preferential
cytotoxic effects against the two breast cancer cell lines,
causing cell cycle delay/arrest and apoptosis. These
effects were accompanied by altered expression of the
cell cycle regulatory proteins, including downregula-
tion of phosphorylated Rb and upregulation of the
CDK inhibitor p27. These effects were likely responsi-
ble for the cell cycle delay/arrest as well as induction of
the apoptotic cascade that manifested in the activation
of caspase 7 and cleavage of PARP in the treated cells.110
Another distinguishing feature of the Banerji
Protocols is the use of both very low and moderately
high potency medicines within the same protocol.
Very low homeopathically prepared potencies would
fall into the mother tincture to 3X range, whereas
moderately high potencies would fall into the 30C to
200C range. Dosing in the protocols is generally more
frequent than in classical homeopathy, again, because
experience has shown this combination pulsed dose
approach to be more effective for cancer than the iso-
lated single-dose method typical of classical homeopa-
thy. It should be clarified that when speaking of the
potency of a homeopathic medicine, the guiding
principle is “less is more,” meaning the more serially
diluted and succussed the medicine, the higher its
potency and apparent duration of action.158
Many of the protocols in use for cancer treatment
involve the use of medicines that are low potency com-
bined with a high potency. Very low potencies are likely
to contain mainly remedy source nanoparticles reduced
and stabilized (capped) by lactose. In nanotechnology,
capping agents stabilize nanoparticles and keep them
from aggregating or agglomerating once formed. Natural
products such as sugars, eg, lactose, honey,159 or ascorbic
acid can serve as nanoparticle-reducing and capping
agents in water-based solutions (Table 1).160,161
In contrast, higher potencies would likely contain
both remedy source nanoparticles and various nano-
silica/nanosilicon structures from repeated rounds of
multiple succussions in ethanolic solutions within
glass containers.69,85,86 As noted elsewhere, evidence
shows that nanosilica and other nanoparticle carriers
can enhance effects of traditional treatments for can-
cers such as snake venoms.103-105,120,162 Silica in nano-
form is also generally effective as an adjuvant to boost
cellular and immune responses to oral and other vac-
cines for various conditions.45,88,90,163,164
Table 3 lists the Banerji protocols in use for some
specific cancers. It is noteworthy that Calcarea phosphori-
ca 3X is included in the protocols for two cancers with
generally very poor prognoses: brain and bone. These
same types of cancers have responded very well to the
Banerji Protocols with cases verified by NCI.1,2,109
Also noteworthy is the occurrence of complete
regressions in a consistent pattern among most of the
cancers treated by the Banerji Protocols. Retrospective
data collected over a 1-year period on patients treated
for lung, brain, and esophageal cancer showed that
complete regressions ranged from 22% to 32% (Figure
4). A similar complete regression of approximately
33% of brain neoplasms, including glioblastoma mul-
tiforme, over a different 1-year period (2010) was
observed after the data in Figure 4 were compiled
(Sarter, unpublished data). Although spontaneous
regressions are a known phenomenon in oncology,
the percentage of complete remissions typically
observed at the Prasanta Banerji Homeopathic
Research Foundation certainly justifies further inves-
tigation of this approach.
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45
INTEGRATIVE NANOMEDICINE CANCER TREATMENT
Review
PULSED DOSING, BIOLOGICAL SIGNALING
MECHANISMS, AND LOW DOSES
Dosing in homeopathy involves the use of low
doses and pulsed intermittent administrations.
Interestingly, mainstream oncology has developed
pulsed dosing regimens for the more toxic chemother-
apy agents to allow recovery of healthy tissue between
treatments. Pulsed dosing is also reported in experi-
mental models using exosomes (endogenous vesicular
nanoparticles) from cancer tumor, dendritic, or malig-
nant ascitic cells for cancer vaccines.38,165 The value of
intermittent doses in homeopathy166,167 may be to take
advantage of the stimulus properties of the treatment
agent and the endogenous adaptive capacity of the
recipient biological system to restore healthier homeo-
static balance.70,113,168,169
A possible objection to the therapeutic value of
homeopathic remedy nanoparticles might be that
Table 3 Exemplars of Banerji Cancer Protocols With Homeopathic Remedies and Potenciesa
Type of Cancer First Line Second Line Third Line Related
Symptoms
Symptomatic
Treatment
Breast cancer Phytolacca 200C 2x/d;
Carcinosin 30C on alternate
nights
Phytolacca 200C 2x/d;
Carcinosin 30C on
alternate nights;
Conium maculatum
3C 2x/d
Thuja occidentalis
30C 2x/d;
Carcinosin 30C every
night
Open ulcer
with offensive
discharge
Psorinum 1000C on
alternate mornings;
Antimonium crudum
200C + Arsenicum
album 200C 4x/d
Osteosarcoma Symphytum 200C and Calcarea
phosphorica 3X, every 3 h alter-
nately;
Carcinosin 30C on alternate
nights
Ruta 200C and
Calcarea phosphorica
3X, every 3 h alter-
nately
Lung metastasis:
Stop Carcinosin
and start:
Kali carbonicum 200C
on alternate days;
Thuja 30C 2x/d
Wound
infection
Hypericum 200C +
Arsenicum album
200C 4x/d
Lung cancer Kali carbonicum 200C on
alternate days;
Thuja 30C 2x/d;
Ferrrum phosphoricum 3X
alternating every 3 h with
Kali muriaticum 3X
Carbo animalis 200C
2x/d;
Bryonia 30C +
Aconitum napellus
200C, 2x/d
Cough
Chest pain
Pleural effusion
Hemoptysis
Ipecacuanha 30C 2
pills every 1-3 h
Hypericum 200C
every 2 h
Lycopodium 30C
liquid 4x/d
Hamamaelis 200C +
Arnica 200C 4x/d
Pancreatic
cancer
Carduus marianus MT and
Conium maculatum 3C liquid
every 3 h alternately;
Chelidonium majus 6X liquid
3x/d
Hydrastis canadensis
MT and
Chelidonium 6X
liquid every 3 h alter-
nately
Pain Belladonna 3C every
10 min
Liver cancer Hydrastis canadensis MT and
Chelidonium majus 6X liquid
every 3 h alternately;
Conium maculatum 3C 2x/d
Myrica MT and
Hydrastis canadensis
MT every 3 h alter-
nately;
Carduus marianus MT
2x/d
Pain
Nausea
Belladonna 3C every
10 min
Tabacum 200C 2x/d or
Ipecacuanha 30C 4x/d
Brain cancer Ruta 6C 2x/d
Calcarea phosphorica
3X 2x/d
Thuja
occidentalis
1000C 1x/wk,
added to first line
Seizures
Headache
Confusion
Vertigo
Edema
Cuprum metallicum
6C + Arnica 3C 2x/d
Picric Acid 200C+
Belladonna 3C every
10 min
Helleborus 30C liquid
2x/d
Conium maculatum
3C 2x/d
Lycopodium 30C
liquid 2x/d
a Notes on nomenclature and dosages:
MT = mother tincture
X = serial dilutions in 1/10 ratios, with each step followed by 10 or more succussions (agitations)
C = serial dilutions in 1/100 ratios, with each step followed by 10 or more succussions (agitations)
All doses are 2 drops of liquid or 2 size #40 pills unless otherwise specified.
“+” indicates that the two medicines are to be mixed together in equal proportions for administration.
46
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GLOBAL ADVANCES IN HEALTH AND MEDICINE
Review
people are constantly exposed to low levels of natural
and manmade nanoparticles without curative effects.
In fact, at higher levels, certain nanoparticles are
toxic and may contribute to various chronic diseas-
es.17,170 However, there are at least three necessary
properties for a given stimulus to initiate endogenous
adaptation and even amplification responses: (1) a
salient and discrete signal that is recognized as a
potential threat to survival of the organism, rising
above (and then falling back to) background noise,
rather than continuous exposure70,112,1113,171-175; (2) a
sufficiently low dose of nanoparticles to serve as a
danger signal or mild environmental stressor without
inducing toxicity: eg a hormetic dose level (see
below)70,168,176,177; and (3) adequate time for the pro-
cesses of cellular and organism adaptation and cross-
adaptation to take hold, amplify effects, and evolve
after cessation of the stimulus.112,178-183
The proposed primary targets of homeopathic
remedies are mediators of the stress response networks
(nervous, endocrine, immune, metabolic) of the
body.70,112 The correct remedies or nanoparticles would
serve as mild stressors to initiate hormesis (biological
adaptation).168,184,185 This conceptualization accom-
modates the use of very low, carefully timed doses.186 It
is also compatible with the work of other investigators
showing that homeopathic remedies171-173 or nanopar-
ticles168,176 can initiate the adaptive process of horme-
sis in an organism. A complex cascade of intracellular
and intercellular biological mediators would carry out
the adaptive changes.112,187,188
Khuda-Bukhsh115 originally proposed modulation
of signal proteins as the mechanism by which homeo-
pathic remedies can produce epigenetic changes and
effects on regulatory pathways in stopping cancer cell
proliferation and inducing apoptosis. Recently we
extended this hypothesis to postulate that the pulsed
dosing approach of homeopathy is a more general treat-
ment strategy. This approach uses the biological signal-
ing properties of remedies to initiate systemic adaptive
changes across the organism as a whole.70,112-114
The ability of nanoparticles to release exo-
somes42,43 offers an initial focus for future research on
homeopathic remedies as biological triggers for salu-
tary responses against cancer. Exosomes have demon-
strated cell-to-cell and systemic signaling proper-
ties.39-42 nanoparticles also can enter cells and activate
intracellular defense cascades44,114 involving inflam-
masomes. Inflammasome protein activation leads to
release of cytokines and other self-regulatory elements
of the immune system.45,89,189
Smaller sized nanosilica (eg, 15 nm diameter) can
produce effects on global genomic hypomethylation,
which might contribute to subtle modulation of epi-
genetic expression.190 Nanosilica also has the capacity
for bottom-up self-assembly of three-dimensional
nanostructure networks built upon biological tem-
plates. These biotemplates include living cells,13,28
proteins,191 collagen,192 and/or DNA12,14,193-195 itself.
Self-assembly processes involving silica in homeopath-
ic remedies might add additional means of amplifying,
reproducing, and transmitting structural and perhaps
electromagnetic information196,197 of specific remedies
in higher potency.
35
30
25
20
15
10
5
0
Bronchogenic Cancer Brain Tumors Oesophageal Cancer All Cases
22.06
19.25
20.66
25.35
12.63
32.13
25.97
20.74
7.1
14.06
28.06
22.14
18.43
20.97
10.49
27.42
22.45
19.91
17.81
12.41
Complete Regression Improved Static Aggravated Expired Discontinued Treatment
Figure 4 Results of treatment of 1132 cases of lung, brain, and esophageal cancers, August 2006 to August 2007.
Source: http://www.pbhrfindia.org/index.php/component/content/archive?year=2011&month=3. Accessed December 3, 2013.
www.gahmj.com • January 2014 • Volume 3, Number 1
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INTEGRATIVE NANOMEDICINE CANCER TREATMENT
Review
Hours of agitation via sonication in different sol-
vents can also create extremely small, light-emitting
tunable silicon nanoparticles (quantum dots).93 Some
silicon nanomaterials already play emerging roles as
not only drug-delivery vehicles,198 but also semicon-
ductors in microelectronics memory, bioimaging, and
nanocatalysis applications.199 The possible role of
homeopathically succussed nanosilicon and nanosilica
per se in retaining and transmitting some of the remedy
source-specific information at higher homeopathic
potencies remains to be explored.196,197
Hormesis is the well-documented phenomenon of
nonlinear dose-response relationships. In hormesis, a
low dose of an agent can stimulate beneficial respons-
es whereas higher doses cause inhibitory or adverse
effects.200 Depending on the nature of the substance,
the dose size cutoff point for defining below the toxic
level or “no observed adverse effect level” (NOAEL) can
vary. In the oncology literature, low dose arsenic has
been found to produce anticancer effects, whereas
higher, more toxic doses can cause cancer.201 Recent
research demonstrates that a nanoform of arsenic tri-
oxide further improves efficacy against breast can-
cer202 and lymphoma while protecting fertility in
mice.119 In homeopathic form, arsenic trioxide is the
widely used remedy Arsenicum album.203-205
Some investigators have proposed that repeated
intermittent mild stressors may improve resilience
against future more intense stressors and foster longev-
ity via epigenetic adaptations.177,188,206 Figure 5 high-
lights the concept of “optimal stress.”207 With suffi-
cient adaptive capacity, an organism can make modest
overcompensations to a mild stressor that counteract
the immediate effects and strengthen it against future
onslaughts. The latter process would involve hormesis.
However, more intense, frequent, or prolonged stress
would instead overwhelm and kill the system or bring
about chronic disease.170,208,209
The Banerji protocols also raise new questions. For
instance, are there differences in effects and/or mecha-
nisms of low- vs high-potency remedies? Are there dif-
ferences in the sizes, shapes, and properties of remedy
nanoparticles at low vs high potencies? The use of low-
potency Calcarea phosphorica in combination with other
higher-potency remedies may provide a generalized
nanoparticulate biological augmentation strategy.
Calcarea phosphorica 3X is a very low-potency form of
calcium phosphate remedy, still well within the range
of homeopathic dilutions that would leave both bulk
form and nanoform source materials together with
Tipping Point
Modest Overcompensation
Minor Avalanche
Ongoing
Homeostatic
Adjustments
Cycles of
Disruption
and Repair
Depletion of
Adaptation
Reserves
Stage 1
Minimal Load
Stage 2
Optimal Load
Stage 3
Overload
Major Avalanche
Time
Level of Complexity
Figure 5 Levels of stress and hormesis, with an optimal stress level that maximally fosters beneficial adaptations. Excessive stress produces
overload and development of disease. Homeopathic remedies at low pulsed doses would act therapeutically on the left side of the curve
to shape adaptive changes, recovery of complexity, and healing. The dosage and size-related properties of the nanoparticles as a mild cel-
lular and systemic stressor, the adaptability of the cells and organism as complex adaptive systems, and the interaction between the rem-
edy nanoparticles and the system determine the type and direction of effects. The analogy is the nonlinear changes that occur in a sand
pile as each grain of sand is added one by one. A single grain of sand arriving at just the critical time can tip the system into an avalanche,
thereby triggering vigorous compensatory adaptive responses. Reprinted with permission from Stark et al, 2012.207
48
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GLOBAL ADVANCES IN HEALTH AND MEDICINE
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mechanically milled lactose78 in any given dose.
Nanomedicine research has repeatedly shown antican-
cer properties of nanoparticulates of this mineral salt
source substance for a variety of cancers, including gli-
oma, osteosarcoma, leukemia, and gastric and liver
malignancies (Table 2).
However, the Banerji protocols also use much
higher potencies of plant and cancer nosode remedies
(ie, more highly diluted and succussed, with only
source nanoparticles and presumably no residual
source bulk form material remaining). Higher remedy
potencies also typically contain glass-derived silica
and/or silicon in bulk and nano forms.85,86 Are there
optimal potencies for eliciting the best anticancer
effects with the lowest risks? Basic science studies on
homeopathic remedies in non-cancer models suggest
that this may be the case.210,211 Consecutive potencies
appear not to exhibit linear dose-response relationships
but rather oscillatory or sinusoidal bidirectional types
of nonlinear curves.211,212
Knowing the composition of a material will not
always reliably predict the nature or direction of its
effects in nanoparticulate form.213 A large body of
research on the properties of top-down manufactured
nanoparticles suggests that their properties are high-
ly sensitive to slight variations in size, shape, defects,
and surface charge.9,22,31,82,97,214 Such structural vari-
ables may be contributing in complex ways to reme-
dy effects and variability from study to study or
patient to patient.112 The complex adaptive network
nature of living systems, including human beings
and animals, adds the likelihood of state-dependent
nonlinear dynamical processes in the nature of the
interactive response to any salient exogenous biologi-
cal signal.70,215 Even conventional nanomaterials can
still convey therapeutic effects at very low doses
when tested.216
Furthermore, the Banerji Protocols use multiple
remedies at the same time, an approach that diverges
from classical homeopathic practice.1 However, the
evidence from mainstream oncology research suggests
the potential therapeutic value of combining multiple
therapies to overcome epigenetic-based resistance to
any single intervention or cancer type.217-219 Studying
the incremental or synergistic effects of various single
vs combinations of remedies on specific cancer cell
lines would therefore be a crucial component of future
research programs in this area. Earlier research on the
combination remedy Canova supports this possibility.
Canova originally contained a fixed combination of
four or five different homeopathic remedies to target
various cancers and infections. The current Canova
formula for immune support in the United States
includes 17 remedies, including homeopathic arsenic
trioxide (Arsenicum Album 17X), a snake venom
(Lachesis mutus 18X), silica (Silicea 18X), and the plant
Thuja occidentalis 16X; see also Table 2).
Human beings have a limited repertoire of ways in
which their bodies can react to stressors or disease pro-
cesses.220 Various cancers, for example, may involve
maturation arrest of pluripotential stem cells and/or
dedifferentiation of mature cells.221,222 Thus, need for
the full person–focused individualization of remedy
selection in classical homeopathy may become clini-
cally less essential in the setting of neoplastic cells. The
Banerji Protocols and other homeopathic cancer treat-
ment programs, therefore, may represent a valid
approach for using homeopathic remedies to address
the usual clinical presentation of a given cancer. In this
type of disease, many patients will show limited, cir-
cumscribed variants of possible mechanisms and symp-
tom manifestations. At the same time, various classical
homeopaths in India and other countries also claim
extraordinary case reports of positive outcomes in indi-
vidualized homeopathic treatment of some of their
own cancer patients.203,223
NEXT STEPS
Existing research expertise on the biological
effects of homeopathic remedies on cancer cells can
inform the design of new nanomedicine studies on
ways to use less toxic natural products in cancer treat-
ment.5 Available data point to the need for studies on
the possible role of exosomes in the initial interface of
homeopathic remedies as nanoparticles conveying
salient biological signals to bodily cells. Comparison of
effects from (1) traditionally made homeopathic rem-
edies such as the mineral salt Calcarea Phosphorica,109
plant remedy Gelsemium sempervirens,64 and the nos-
ode breast cancer tumor remedy Carcinosin110 with (2)
modern nanoparticles such as calcium phosphate
nanoparticles,31 nano-encapsulated Gelsemium
extract,65 and breast cancer tumor–derived exosomes6
would be useful. Techniques such as nanoparticle
tracking analysis,224,225 scanning electron microscopy,
and ultraviolet visual and Raman spectroscopy226,227
combined with fluorescent-labeled antibodies provide
contemporary research tools to evaluate and character-
ize exosomes released during cell interactions with
remedies and nanoparticulates.225,228,229
Finally, although the Banerji Protocols from India
involve more diagnosis-related remedy selection than
classical homeopathy, they still employ a flexible,
albeit limited, set of remedies, partially individualized
in their approach to specific types of cancers and associ-
ated symptoms. From a public health perspective, the
Banerji approach strikes a pragmatic balance between
the ideals of complete individualization of remedy
selection in classical homeopathic constitutional pre-
scribing71 and the need for broader accessibility of
homeopathic treatment to large, often indigent, popu-
lations worldwide.
The systemization of the Banerji approach also
might permit dissemination to busy integrative clini-
cians who may lack the years of detailed homeopathic
education needed for accurate constitutional remedy
selection and case management in classical homeo-
pathic practice.147 A larger number of integrative
www.gahmj.com • January 2014 • Volume 3, Number 1
49
INTEGRATIVE NANOMEDICINE CANCER TREATMENT
Review
healthcare providers can learn the essential decision
trees of the Banerji Protocols1 as compared with classic
alhomeopathy. Nonetheless, systematic comparative
effectiveness studies of the Banerji Protocols vs (1)
fully individualized classical homeopathic treatment
and (2) conventional drugs and radiation treatment
would better reveal the optimal clinical strategies.
Key next steps for preclinical and clinical research
could involve the following.
•Replicating and extending electron microscopy
studies on homeopathic remedies in independent
laboratories to focus on Banerji Protocol remedies
and specific homeopathic remedies previously
demonstrated to exhibit antineoplastic effects in
vitro or in vivo.
•Systematically applying widely used nanoparticle
characterization methods to evaluate effects of
varying pH, temperature, ethanol concentration,
dilution procedures, succussion methods, glass-
ware, and age of solution on the size, shape, stabil-
ity, and biological effects of nanoparticles in
specific homeopathic remedies made from plants,
minerals, animal venoms, and malignant tumor
cells. Methods would include
−measuring particle zeta potentials, dynamic light
scattering (DLS), and conducting nanoparticle
tracking analysis (NTA) of remedies192,224,230 and
−characterizing and comparing homeopathic
medicine potencies found most effective in
the Banerji protocols1,216 with other potencies
of the “same” medicine, given evidence in pre-
vious research that all potencies of a given
agent are not comparably active231,232 and
that nanocluster size can lead to nonlinear
dose-response findings.22
•Identifying biochemical or physiological biomark-
ers used in conventional cancer research to use for
testing dose-response relationships of specific
homeopathic remedies.
−A wide range of doses from possible beneficial
hormetic range to toxic should be evaluated.
−Exosome release, inflammasome proteins and
cytokine activation patterns are possible biomark-
er candidates in addition to known mediators
involved in blocking cancer cell proliferation and
facilitating apoptosis of malignant cells.
•Using cell culture and animal models to deter-
mine the comparative advantages and disadvan-
tages of homeopathically prepared vs modern
manufactured nanoparticle forms and doses of
specific natural products found most promising
from outcomes study data.
•Pursuing clinical outcomes studies, comparative
effectiveness trials, and randomized controlled
trials based on the most promising Banerji
Protocols for specific cancers. Candidate condi-
tions include brain tumors (gliomas, glioblasto-
mas multiforme) and osteosarcomas.
CONCLUSIONS
The overlaps between the manufacturing, nature,
and properties of nanoparticles and those of homeo-
pathic remedies merit additional examination.70,112-114
Given the recent empirical findings of source nanopar-
ticles at low and high potencies of metal68 and plant69
homeopathic remedies and even some homeopathi-
cally prepared conventional drugs,212 the similarities
in effects of nanoparticles and homeopathic remedies
on cancer cell lines add rationale for further investiga-
tion. The fact that many homeopathic remedies begin
as source materials milled/ground in lactose for hours
makes initial generation of top-down nanoparticles
obligatory.98 The documented ability of (1) succus-
sions to release silica and nanosilica from the inside
walls of glassware85 and (2) plant mother tinctures to
biosynthesize nanoparticles from silica55 or metal pre-
cursors9,233 in solution offer additional routes for mak-
ing other types of nanoparticles in liquid remedies.
Succussions, like sonication,84 could also disperse larg-
er nanoparticles into smaller particles.
Once formed, nanoparticles accumulate heteroge-
neously in colloidal solution and are transferred from
container to container after succussions during homeo-
pathic manufacturing procedures.67 These data empiri-
cally address the main historical objection of skeptics
to the persistence of specific source material in higher
homeopathic dilutions. Based on nanotechnology,214 it
is also possible that either (1) the remedy nanoparticles
attach to, coat, dope, and/or modify the silica and sili-
con nanoparticles at the “higher” liquid potencies or (2)
some silica nanoparticles form shells around the reme-
dy source nanoparticle cores as templates. With or
without attachment of remedy source materials to sili-
ca and/or silicon nanoparticles, nonhomeopathy stud-
ies show that silica nanoparticles85 can augment anti-
cancer effects of traditional natural products such as
snake venom103-105 and activate heightened immune
responsivity to very low quantities of antigens164 and
vaccines overall.88,89
Overall, the Banerji cancer protocols raise integra-
tive healthcare possibilities for blending the traditional
clinical wisdom of experienced homeopathic practitio-
ners from India on how to select and dose nanoparticu-
lates for cancer treatment with the advanced contem-
porary methods of manufacturing nanoparticles using
more replicable modern nanotechnology. Together,
these concepts and tools suggest the possibility of accel-
erating evidence-based advances in natural product
nanomedicine for treatment of people with cancer.
AUTHORS’ CONTRIBUTIONS
This article began with discussions among the
authors about the Banerji protocols and their interest in
pursuing systematic and rigorous research to follow up
the National Cancer Institute Best Case Series findings.
IRB initially drafted the article; BS, PB, and PB drafted the
section on the Banerji Protocols. MK edited the article
for clarity and context of integrative cancer care in com-
Acknowledgment
This study was supported
in part by National Center
for Complementary and
Alternative Medicine
grant T32 AT01287
(PI: IRB).
50
Volume 3, Number 1 • January 2014 • www.gahmj.com
GLOBAL ADVANCES IN HEALTH AND MEDICINE
Review
plex adaptive systems. SJ and JI edited the information
on biological effects of nanoparticles and homeopathic
remedies. All authors edited, revised, and approved the
final article.
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