Charles Jeffrey Brinker

• University of New Mexico

The safety of inorganic nanoparticles (NPs) remains a critical challenge for their clinical translation. To address this, we developed a machine-learning (ML) framework that predicts NP toxicity both in vitro and in vivo, leveraging physicochemical properties and experimental conditions. A curated in vitro cytotoxicity dataset was used to train and...

Despite encouraging outcomes of the eight FDA approved drugs in lessening obesity burden, they have been associated with side effects caused by the lack of direct action on the adipose tissue. Therefore, a nanomedicine is reported that promotes the transformation of local fat‐storage white adipocytes, associated with obesity, into thermogenic adipo...

The concurrent preservation of morphological, structural, and genomic attributes within biological samples is paramount for comprehensive insights into biological phenomena and disease mechanisms. However, current preservation methodologies (e.g., cryopreservation, chemical reagent fixation, and bioplasticization) exhibit limitations in simultaneou...

The growing world population and increasing life expectancy are driving the need to improve the quality of blood transfusion, organ transplantation, and preservation. Here, to improve the ability of red blood cells (RBCs) for normothermic machine perfusion, a biocompatible blood silicification approach termed “shielding-augmenting RBC-in-nanoscale...

Background Salmonellosis, caused by Salmonella enterica serovar Typhimurium, is a significant global threat. Host immunity limits bacterial replication by inducing hepcidin, which degrades ferroportin, reducing iron transfer. However, this boosts macrophage iron storage, aiding intracellular pathogens like Salmonella. Mice lacking ferritin heavy ch...

The ability to finely tune/balance the structure and rigidity of enzymes to realize both high enzymatic activity and long‐term stability is highly desired but highly challenging. Herein, we propose the concept of the “silicazyme”, where solid inorganic silica undergoes controlled hybridization with the fragile enzyme under moderate conditions at th...

The ability to finely tune/balance the structure and rigidity of enzymes to realize both high enzymatic activity and long‐term stability is highly desired but highly challenging. Herein, we propose the concept of the “silicazyme”, where solid inorganic silica undergoes controlled hybridization with the fragile enzyme under moderate conditions at th...

Salmonellosis is a severe infection caused by Salmonella enterica serovar Typhimurium, leading to significant global morbidity and mortality. Host nutrition immunity restricts extracellular bacterial replication by reducing iron availability through the induction of the antimicrobial hormone hepcidin. Hepcidin degrades the iron exporter ferroportin...

Salmonellosis, caused by Salmonella enterica serovar Typhimurium, is a significant global threat. Host immunity limits bacterial replication by inducing hepcidin, which degrades ferroportin, reducing iron transfer. However, this boosts macrophage iron storage, aiding intracellular pathogens like Salmonella. Mice lacking ferritin heavy chain (FTH1)...

Hyperuricemia, caused by an imbalance between the rates of production and excretion of uric acid (UA), may greatly increase the mortality rates in patients with cardiovascular and cerebrovascular diseases. Herein, for fast‐acting and long‐lasting hyperuricemia treatment, armored red blood cell (RBC) biohybrids, integrated RBCs with proximal, cascad...

Owing to their uniform and tunable particle size, pore size, and shape, along with their modular surface chemistry and biocompatibility, mesoporous silica nanoparticles (MSNs) have found extensive applications as nanocarriers to deliver therapeutic, diagnostic and combined "theranostic" cargos to cells and tissues. Although thoroughly investigated,...

The vascular endothelium from individual organs is functionally specialized, and it displays a unique set of accessible molecular targets. These serve as endothelial cell receptors to affinity ligands. To date, all identified vascular receptors have been proteins. Here, we show that an endothelial lung-homing peptide (CGSPGWVRC) interacts with C16-...

To increase the red blood cell (RBC) cryopreservation efficiency by metal–organic frameworks (MOFs), a dimensional reduction approach has been proposed. Namely, 3D MOF nanoparticles are progressively reduced to 2D ultra‐thin metal–organic layers (MOLs). We found that 2D MOLs are beneficial for enhanced interactions of the interfacial hydrogen‐bonde...

To increase the red blood cell (RBC) cryopreservation efficiency by metal–organic frameworks (MOFs), a dimensional reduction approach has been proposed. Namely, 3D MOF nanoparticles are progressively reduced to 2D ultra‐thin metal–organic layers (MOLs). We found that 2D MOLs are beneficial for enhanced interactions of the interfacial hydrogen‐bonde...

Impaired autophagy, a cellular digestion process that eliminates proteins and damaged organelles, has been implicated in neurodegenerative diseases, including motor neuron disorders. Motor neuron targeted upregulation of autophagy may serve as a promising therapeutic approach. Lanthionine ketenamine (LK), an amino acid metabolite found in mammalian...

Extracellular vesicles (EVs) can facilitate essential communication among cells in a range of pathophysiological conditions including cancer metastasis and progression, immune regulation, and neuronal communication. EVs are membrane-enclosed vesicles generated through endocytic origin and contain many cellular components, including proteins, lipids...

We postulate that nanoparticles (NPs) for use in therapeutic applications have largely not realized their clinical potential due to an overall inability to use in vitro results to predict NP performance in vivo. The avian embryo and associated chorioallantoic membrane (CAM) has emerged as an in vivo preclinical model that bridges the gap between in...

Deoxyribonucleic acid (DNA) is the blueprint of life, and cost-effective methods for its long-term storage could have many potential benefits to society. Here we present the method of in situ cryosilicification of whole blood cells, which allows long-term preservation of DNA. Importantly, our straightforward approach is inexpensive, reliable, and y...

Mineralization is a natural process that constructs intricate structures at diverse interfaces, but with poor controllability. Herein, we present an alternative strategy for dynamic control of nano-scale mineralization processes and the subsequent construction of an all-in-one healing agent to meet the requirements of wound healing with complex phy...

The triple-negative breast cancer (TNBC) microenvironment makes a feature of aberrant vasculature, high interstitial pressure, and compact extracellular matrix, which combine to reduce the delivery and penetration of therapeutic agents, bringing about incomplete elimination of cancer cells. Herein, employing the tumor penetration strategy of size-s...

Unhealed wound after malignant skin tumor resection, characterized by full‐thickness cutaneous defects, large open cavities, and incomplete tumor tissue resection are the leading cause for long recovery times, poor prognoses, and high recurrence among patients. Herein, a hyaluronic acid (HA)‐based microneedle (MN) functionalized with biomineralized...

Siliceous nanomaterials are attractive candidates for applications in cancer theranostics due to their precise synthesis control, ease of surface functionalization, accuracy of characterization, controllable release of cargo, and predictable pharmacokinetics. However, the inorganic silica core inherent to these nanomaterials has colloidal instabili...

Fumed silica nanoparticles (FSN) are one of the most common synthetic forms of silica, but prolonged exposure leads to cell toxicity and apoptosis due to reactive oxygen species (ROS) generation and cell membrane perturbation resulting from hydrogen bonding and electrostatic interactions. Increasing attention is being put on synthesizing FSN materi...

In nature, biosilicification directs the formation of elaborate amorphous silica exoskeletons that provide diatoms mechanically strong, chemically inert, non-decomposable silica armor conferring chemical and thermal stability as well as resistance to microbial attack, without changing the optical transparency or adversely effecting nutrient and was...

Cell cryopreservation is of vital significance both for transporting and storing cells before experimental/clinical use. Cryoprotectants (CPAs) are necessary additives in the preserving medium in cryopreservation, preventing cells from freeze-Thaw injuries. Traditional organic solvents have been widely used in cell cryopreservation for decades. Giv...

In article number 2005935, Wei Zhu, Stefan Wuttke, C. Jeffrey Brinker, and co‐workers assemble native red blood cells (RBCs) within and protected by functional exoskeletons of interlinked MOF nanoparticles. The armored RBCs preserve the original properties of RBCs (oxygen storage) and inherit the exogenous properties of functionalizing nanoparticle...

The structural modulation of multicompartment porous nanomaterials is one of the major challenges of nanoscience. Herein, by utilizing the polyhedral effects/characteristics of metal-organic frameworks (MOFs), we present a versatile approach to construct MOF-organosilica hybrid branched nanocomposites with MOF cores, SiO2 shells, and periodic mesop...

Nanoscale transport using the kinesin-microtubule system has been successfully used in applications ranging from self-assembly, to biosensing, to biocomputation. Realization of such applications necessitates robust microtubule motility particularly in the presence of complex sample matrices that can affect the interactions of the motors with the su...

Bio/artificial hybrid nanosystems based on biological matter and synthetic nanoparticles (NPs) remain a holy grail of materials science. Herein, inspired by the well‐defined metal–organic framework (MOF) with diverse chemical diversities, the concept of “armored red blood cells” (armored RBCs) is introduced, which are native RBCs assembled within a...

Simple Summary A challenge for Nanomedicine is delivery to the site of action, most commonly the tumor microenvironment. When injected systemically, scavenger cells, such as macrophages, rapidly sequester nanoparticles. This study asks if macrophages can directly deliver scavenged nanoparticles to cancer cells via cellular connections known as tunn...

Natural silica and silicates are predominantly crystalline and constitute the most abundant components of the Earth’s crust. Man-made silica is typically amorphous and manufactured in tonnage quantities for commercial use and, more recently, for burgeoning medical applications, making synthetic amorphous silica nanoparticles (SASNs) arguably the mo...

CRISPR gene editing technology is strategically foreseen to control diseases by correcting underlying aberrant genetic sequences. In order to overcome drawbacks associated with viral vectors, the establishment of an effective non-viral CRISPR delivery vehicle has become an important goal for nanomaterial scientists. Herein, we introduce a monosized...

The design and synthesis of artificial materials that mimic the structures, mechanical properties, and ultimately functionalities of biological cells remains a current holy grail of materials science. Here, based on a silica cell bioreplication approach, we report the design and construction of synthetic rebuilt red blood cells (RRBCs) that fully m...

While plasma concentration kinetics has traditionally been the predictor of drug pharmacological effects, it can occasionally fail to represent kinetics at the site of action, particularly for solid tumors. This is especially true in the case of delivery of therapeutic macromolecules (drug‐loaded nanomaterials or monoclonal antibodies), which can e...

Porous silica‐based materials have burgeoning applications ranging from fillers and additives, to adsorbents, catalysts, and recently therapeutic agents and vaccines in nanomedicine. The preponderance of these materials is made by sol–gel processing wherein soluble silica precursors are reacted to form amorphous networks composed of siloxane bonds....

Towards clinical translation of cancer nanomedicine, it is important to systematically investigate the various parameters related to nanoparticle (NP) physicochemical properties, tumor characteristics, and inter-individual variability that affect the tumor delivery efficiency of therapeutic nanomaterials. Comprehensive investigation of these parama...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Following our call to join in the discussion over the suitability of implementing a reporting checklist for bio–nano papers, the community responds. Below we report short extracts highlighting the main messages of the correspondences we received.

Creating a synthetic exoskeleton from abiotic materials to protect delicate mammalian cells and impart them with new functionalities could revolutionize fields like cell‐based sensing and create diverse new cellular phenotypes. Herein, the concept of “SupraCells,” which are living mammalian cells encapsulated and protected within functional modular...

The development of hybrid nanomaterials mimicking antifreeze proteins that can modulate/inhibit the growth of ice crystals for cell/tissue cryopreservation has attracted increasing interests. Herein, we describe the first utilization of zirconium (Zr)-based metal-organic framework (MOF) nanoparticles (NPs) with well-defined surface chemistries for...

Cancer continues to be among the leading healthcare problems worldwide, and efforts continue not just to find better drugs, but also better drug delivery methods. The need for delivering cytotoxic agents selectively to cancerous cells, for improved safety and efficacy, has triggered the application of nanotechnology in medicine. This effort has pro...

A novel and modular super‐assembly approach combines the synergistic advantages of metal–organic cage super‐assemblies (e.g., highly controlled architecture, high payloads of multiple cargos) and micelles (e.g., low inherent toxicity) for targeted drug delivery is presented by Wei Zhu, C. Jeffrey Brinker, and co‐workers in article number 1806774. B...

In clinical breast cancer intervention, selection of the optimal treatment protocol based on predictive biomarkers remains an elusive goal. Here, we present a modeling tool to predict the likelihood of breast cancer response to neoadjuvant chemotherapy using patient specific tumor vasculature biomarkers. A semi-automated analysis was implemented an...

Supported ultrasmall noble metal nanocluster (UNMN)-based catalysts are one of the most important classes of solid materials for heterogeneous catalysis. In this work, we present a novel strategy for the controlled synthesis of ligand free-UNMN nanocatalysts based on in-situ reduction of a palladium (Pd)-based metal-organic cage (MOC) confined with...

Targeted drug delivery remains at the forefront of biomedical research but remains a challenge to date. Herein, the first superassembly of nanosized metal–organic polyhedra (MOP) and their biomimetic coatings of lipid bilayers are described to synergistically combine the advantages of micelles and supramolecular coordination cages for targeted drug...

The progress of nanoparticle (NP)-based drug delivery has been hindered by an inability to establish structure-activity relationships in vivo. Here, using stable, monosized, radiolabeled, mesoporous silica nanoparticles (MSNs), we apply an integrated SPECT/CT imaging and mathematical modeling approach to understand the combined effects of MSN size,...

Venezuelan equine encephalitis virus (VEEV) poses a major public health risk due to its amenability for use as a bioterrorism agent and its severe health consequences in humans. ML336 is a recently developed chemical inhibitor of VEEV, shown to effectively reduce VEEV infection in vitro and in vivo. However, its limited solubility and stability cou...

Silica-based nanomaterials are extensively used in industrial applications and academic biomedical research, thus properly assessing their toxicity and biodegradability is essential for their safe and effective formulation and use. Unfortunately, there is often a lot of confusion in the literature with respect to the toxicity and biodegradability o...

Lipid-coated mesoporous silica nanoparticles (LC-MSNs) have recently emerged as a next-generation cargo delivery nanosystem combining the unique attributes of both the organic and inorganic components. The high surface area biodegradable inorganic mesoporous silica core can accommodate multiple classes of bio-relevant cargos in large amounts, while...

The original version of this Article contained an error in the spelling of the author Stanley S. Chou, which was incorrectly given as Stan Chou. This has now been corrected in both the PDF and HTML versions of the Article.

Nanoparticles have shown great promise in improving cancer treatment efficacy while reducing toxicity and treatment side effects. Predicting the treatment outcome for nanoparticle systems by measuring nanoparticle biodistribution has been challenging due to the commonly unmatched, heterogeneous distribution of nanoparticles relative to free drug di...

A novel strategy for the versatile functionalization of the external surface of metal-organic frameworks (MOFs) has been developed based on the direct coordination of a phenolic-inspired lipid molecule DPGG (1,2-dipalmitoyl-sn-glycero-3-galloyl) with metal nodes/sites surrounding MOF surface. X-ray diffraction and Argon sorption analysis prove that...

The limited flux and selectivities of current carbon dioxide membranes and the high costs associated with conventional absorption-based CO2 sequestration call for alternative CO2 separation approaches. Here we describe an enzymatically active, ultra-thin, biomimetic membrane enabling CO2 capture and separation under ambient pressure and temperature...

Silsesquioxane nanoparticles are composed of repetitive organosilica fragments in their frameworks and are now recognized to have outstanding functional fertility. Depending on the organosilane and the synthetic pathways, silsesquioxane NPs can be pendant, bridged, dense or porous. Recently the diverse functionalities of mesoporous silsesquioxane n...

Cholera toxin B (CTB) modified mesoporous silica nanoparticle supported lipid bilayers (CTB-protocells) are a promising, customizable approach for targeting therapeutic cargo to motoneurons. In the present study, the endocytic mechanism and intracellular fate of CTB-protocells in motoneurons was examined to provide information for the development o...

Supplementary Figures, Supplementary Tables and Supplementary Methods

B.-L.S. acknowledges the Chinese Central Government for an ‘Expert of the State’ position in the Program of the ‘Thousand Talents’ and a Life membership at Clare Hall, University of Cambridge. Y.L. acknowledges Hubei Provincial Department of Education for the ‘Chutian Scholar’ program. T.H. acknowledges support from the Royal Academy of Engineering...

In order to design hybrid cellular/synthetic devices such as sensors and vaccines, it is important to understand how the metabolic state of living cells changes upon physical confinement within three-dimensional matrices. We analyze the gene expression patterns of stationary phase Saccharomyces cerevisiae (S. cerevisiae) cells encapsulated within t...

Contrary to the notion that the use of fumed silica in consumer products can "generally (be) regarded as safe" (GRAS), the high surface reactivity of pyrogenic silica differs from other forms of synthetic amorphous silica (SAS), including the capacity to induce acute membrane damage and acute pro-inflammatory changes in the murine lung. In addition...

Many nanocarrier cancer therapeutics currently under development, as well as those used in the clinical setting, rely upon the enhanced permeability and retention (EPR) effect to passively accumulate in the tumor microenvironment and kill cancer cells. In leukemia, where leukemogenic stem cells and their progeny circulate within the peripheral bloo...

Significance The main goal in the emerging field of cancer nanomedicine is to generate, standardize, and produce multifunctional carriers designed to improve the response of drugs against tumors. Here we report the design, development, and preclinical validation of a ligand-directed bioinorganic platform that integrates tumor targeting, receptor-me...

Mesoporous silica nanoparticle-supported lipid bilayers, termed 'protocells,' represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single 'magic bullet'. Consequently, the protocell has been designed as a modula...

Nanomedicines have significant potential for cancer treatment. Although the majority of nanomedicines currently tested in clinical trials utilize simple, biocompatible liposome-based nanocarriers, their widespread use is limited by non-specificity and low target site concentration and thus, do not provide a substantial clinical advantage over conve...

The remarkable impact encapsulation matrix chemistry can have on the bioactivity and viability of integrated living cells is reported. Two silica chemistries (aqueous silicate and alkoxysilane), and a functional component additive (glycerol), are employed to generate three distinct silica matrices. These matrices are used to encapsulate living E. c...

Establishing processing-structure-property relationships for monolayer materials is crucial for a range of applications spanning optics, catalysis, electronics and energy. Presently, for molybdenum disulfide, a promising catalyst for artificial photosynthesis, considerable debate surrounds the structure/property relationships of its various allotro...

Three-dimensional (3D) cell cultures produce more in vivo-like multicellular structures such as spheroids that cannot be obtained in two-dimensional (2D) cell cultures. Thus, they are increasingly employed as models for cancer and drug research, as well as tissue engineering. It has proven challenging to stabilize spheroid architectures for detaile...

Despite significant progress in development of bioanalytical devices cost, complexity, access to reagents and lack of infrastructure have prevented use of these technologies in resource-limited regions. To provide a sustainable tool in the global effort to combat infectious diseases the diagnostic device must be low cost, simple to operate and read...

The production of pyrogenic (fumed) silica is increasing worldwide at a 7% annual growth rate, including expanded use in food, pharmaceuticals and other industrial products. Synthetic amorphous silica, including fumed silica, has been generally recognized as safe (GRAS) for use in food products by the Food and Drug Administration (FDA). However, em...

The production of pyrogenic (fumed) silica is increasing worldwide at a 7% annual growth rate, including expanded use in food, pharmaceuticals, and other industrial products. Synthetic amorphous silica, including fumed silica, has been generally recognized as safe for use in food products by the Food and Drug Administration. However, emerging evide...

Every chemist, material scientist, physicist, engineer, or commercial enterprise involved in the synthesis and/or production of engineered nanomaterials (ENM) or nano-enabled products aspires to develop safe materials. Nanotechnology environmental health and safety (nanoEHS) is a research discipline that involves the study of the possible adverse h...

Three-dimensional encapsulation of cells within nanostructured silica gels or matrices enables applications as diverse as biosensors, microbial fuel cells, artificial organs, and vaccines; it also allows the study of individual cell behaviors. Recent progress has improved the performance and flexibility of cellular encapsulation, yet there remains...