Burke, A. et al. Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation. Proc. Natl Acad. Sci. USA 106, 12897-12902

Department of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2009; 106(31):12897-902. DOI: 10.1073/pnas.0905195106
Source: PubMed


Multiwalled carbon nanotubes (MWCNTs) exhibit physical properties that render them ideal candidates for application as noninvasive mediators of photothermal cancer ablation. Here, we demonstrate that use of MWCNTs to generate heat in response to near-infrared radiation (NIR) results in thermal destruction of kidney cancer in vitro and in vivo. We document the thermal effects of the therapy through magnetic resonance temperature-mapping and heat shock protein-reactive immunohistochemistry. Our results demonstrate that use of MWCNTs enables ablation of tumors with low laser powers (3 W/cm(2)) and very short treatment times (a single 30-sec treatment) with minimal local toxicity and no evident systemic toxicity. These treatment parameters resulted in complete ablation of tumors and a >3.5-month durable remission in 80% of mice treated with 100 microg of MWCNT. Use of MWCNTs with NIR may be effective in anticancer therapy.

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    • "Further, ionizing radiation is generally not recommended, although radiosurgery boost has been used in some selected situations (5). Photothermal treatment is an alternative therapy, which induces cytotoxicity to drug-sensitive and -resistant tumor cells (6). This therapy involves the induction of hyperthermia, defined as temperatures above 40°C. "
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    ABSTRACT: The objective was to use carbon nanotubes (CNT) coupled with near-infrared radiation (NIR) to induce hyperthermia as a novel non-ionizing radiation treatment for primary brain tumors, glioblastoma multiforme (GBM). In this study, we report the therapeutic potential of hyperthermia-induced thermal ablation using the sequential administration of carbon nanotubes (CNT) and NIR. In vitro studies were performed using glioma tumor cell lines (U251, U87, LN229, T98G). Glioma cells were incubated with CNTs for 24 h followed by exposure to NIR for 10 min. Glioma cells preferentially internalized CNTs, which upon NIR exposure, generated heat, causing necrotic cell death. There were minimal effects to normal cells, which correlate to their minimal uptake of CNTs. Furthermore, this protocol caused cell death to glioma cancer stem cells, and drug-resistant as well as drug-sensitive glioma cells. This sequential hyperthermia therapy was effective in vivo in the rodent tumor model resulting in tumor shrinkage and no recurrence after only one treatment. In conclusion, this sequence of selective CNT administration followed by NIR activation provides a new approach to the treatment of glioma, particularly drug-resistant gliomas.
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    • "R. Vankayala et al. / Biomaterials xxx (2014) 1e12 6 Please cite this article in press as: Vankayala R, et al., Gold nanoshells-mediated bimodal photodynamic and photothermal cancer treatment using ultra-low doses of near infra-red light, Biomaterials (2014), cells (see Fig. 5). Among various nanoshells, gold nanorod-in shells induce slightly higher levels of HSP 70 under 550 and 940 nm light irradiation [45] [46]. It is well understood that the photothermal effects can be significantly suppressed by lowering down the medium temperature from 37 to 4 C, since the photothermal heating effects initiate apoptosis processes only after reaching a local intracellular threshold temperature of 42e45 C, and lasting for 15e60 min or higher than 50 C for 4e6 min [47]. "
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    ABSTRACT: Previously, gold nanoshells were shown to be able to effectively convert photon energy to heat, leading to hyperthermia and suppression of tumor growths in mice. Herein, we show that in addition to the nanomaterial-mediated photothermal effects (NmPTT), gold nanoshells (including, nanocages, nanorod-in-shell and nanoparticle-in-shell) not only are able to absorb NIR light, but can also emit fluorescence, sensitize formation of singlet oxygen and exert nanomaterial-mediated photodynamic therapeutic (NmPDT) complete destruction of solid tumors in mice. The modes of NmPDT and NmPTT can be controlled and switched from one to the other by changing the excitation wavelength. In the in vitro experiments, gold nanocages and nanorod-in-shell show larger percentage of cellular deaths originating from NmPDT along with the minor fraction of NmPTT effects. In contrast, nanoparticle-in-shell exhibits larger fraction of NmPTT-induced cellular deaths together with minor fraction of NmPDT-induced apoptosis. Fluorescence emission spectra and DPBF quenching studies confirm the generation of singlet O2 upon NIR photoirradiation. Both NmPDT and NmPTT effects were confirmed by measurements of reactive oxygen species (ROS) and subsequent sodium azide quenching, heat shock protein expression (HSP 70), singlet oxygen sensor green (SOSG) sensing, changes in mitochondria membrane potential and apoptosis in the cellular experiments. In vivo experiments further demonstrate that upon irradiation at 980 nm under ultra-low doses (∼150 mW/cm(2)), gold nanocages mostly exert NmPDT effect to effectively suppress the B16F0 melanoma tumor growth. The combination of NmPDT and NmPTT effects on destruction of solid tumors is far better than pure NmPTT effect by 808 nm irradiation and also doxorubicin. Overall, our study demonstrates that gold nanoshells can serve as excellent multi-functional theranostic agents (fluorescence imaging + NmPDT + NmPTT) upon single photon NIR light excitation under ultra-low laser doses.
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    • "This is so for a number of reasons: (i) poor controllability of inhalation exposure; (ii) less cytotoxicity of water-soluble CNTs than non-functionalized particles [4]; and more importantly, (iii) functionalized CNTs have shown exciting bioapplications . For example, engineered carbon nanotubes (CNTs) have been extensively utilized as cancer theranostics [1], serving as composite nanomaterials for cancer imaging [5], drug loading [6] [7], and photothermal therapy [8] [9]. "
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    ABSTRACT: In many cases cancer is caused by gene deficiency that is being passed along from generation to generation. Soluble carbon nanotubes (CNTs) have shown promising applications in the diagnosis and therapy of cancer, however, the potential relationship between cancer-prone individuals and response to CNT exposure as a prerequisite for development of personalized nanomedicine, is still poorly understood. Here we report that intravenous injections of multi-walled carbon nanotubes into p53 (a well-known cancer-susceptible gene) heterozygous pregnant mice can induce p53- dependent responses in fetal development. Larger sized multi-walled carbon nanotubes moved across the blood-placenta barrier (BPB), restricted the development of fetuses, and induced brain deformity, whereas single-walled and smaller sized multi-walled carbon nanotubes showed no or less fetotoxicity. A molecular mechanism study found that multi-walled carbon nanotubes directly triggered p53-dependent apoptosis and cell cycle arrest in response to DNA damage. Based on the molecular mechanism, we also incorporated N-acetylcysteine (NAC), an FDA approved antioxidant, to prevent CNTs induced nuclear DNA damage and reduce brain development abnormalities. Our findings suggest that CNTs might have genetic background-dependent toxic effect on the normal development of the embryo, and provide new insights into protection against nanoparticle-induced toxicity in potential clinical applications.
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