Nanotechnology for cancer treatment

Abstract

Nanotechnology has the potential to increase the selectivity and potency of chemical, physical, and biological approaches for eliciting cancer cell death while minimizing collateral toxicity to nonmalignant cells. Materials on the nanoscale are increasingly being targeted to cancer cells with great specificity through both active and passive targeting. In this review, we summarize recent literature that has broken new ground in the use of nanotechnology for cancer treatment with an emphasis on targeted drug delivery.

1 Introduction

The need for an advanced technology to play an important role for cancer treatment is clearly evident in the statistics indicating that cancer incidence, prevalence, and mortality remain at exceedingly high levels [1]. Cancer is one of the leading causes of deaths worldwide with an estimated 7.6 million individuals lost each year and accounting for 13% of all deaths. Cancer-related mortality is expected to rise to 13.1 million by 2030. Cancer is not a single disease but a multitude of diseases with each organ or system developing a distinct set of diseases. Many instances of cancer could be avoided, with some estimates indicating that about 30% of cancer deaths are associated with smoking or other lifestyle factors or dietary practices that could potentially be avoided by changes in human behavior [2–4]. Nonetheless, the majority of cancers cannot be avoided by simple behavioral changes and require technological innovation to improve outcomes. The developed world has had notable success in limiting cancer caused by viral infections [e.g., human papilloma virus (HPV)] [5–7]. This success could be further enhanced by more widespread implementation of existing vaccine technologies and also by using nanotechnology as well as other technologies to improve vaccination efficiency [5–8]. Nanotechnology may also be able to increase the percentage of cancers that are diagnosed early through improved imaging and this, in conjunction with more aggressive implementation of existing screening technologies, will lead to improved outcomes for cancer patients [9, 10]. Still, for many cancer types, new approaches for treating established disease are required. To address these therapeutic requirements, nano-sized molecular tools capable of distinguishing between malignant and nonmalignant cells as well as delivering a lethal payload should be developed. This review summarizes several of the most innovative technologies that have been reported in recent years and that hold promise for improving outcomes for cancer patients.

2 Tumor targeting

One of the potential fundamental advantages of nanotechnology for cancer treatment is tumor targeting (Figure 1). The ability to differentiate malignant cells from nonmalignant and to selectively eradicate malignant cells is central to the mission of nanotechnology as it relates to cancer treatment. Two fundamental processes are involved in differentiating malignant and nonmalignant cells: passive and active targeting. Passive targeting takes advantage of the enhanced permeability and retention (EPR) effect [11, 12] to increase the concentration of nanoparticles (NPs) in the tumor. Active targeting [13] may involve selective molecular recognition of antigens, frequently proteins, that are expressed on the surfaces of cancer cells in order to localize NPs to malignant cells or, alternatively, exploits biochemical properties associated with malignancy such as matrix metalloproteinase secretion [14]. Passive and active targeting may be deployed independently, or the two approaches may be combined. Both strategies benefit from surface modifications of NPs that minimize uptake by the macrophage phagocytic system (MPS) [15], thus, maximizing time in circulation.

Figure 1.

Depiction of NP targeting of malignant cells through both active and passive targeting. NPs (green stars) accumulate in tumor tissue via the EPR – a form of passive targeting. Inset – shape-specific interaction of the NPs with cell-surface receptors is indicated by “Y-star” interactions that represent active targeting of NPs to cancer cells based upon specific molecular interactions.

2.1 Passive targeting via the EPR

It is well known that the tumor vasculature is leaky relative to the hierarchical structure of normal vasculature, in part, because malignant cells are not responsive to cell signaling required for orderly vasculogenesis [16, 17]. Macromolecules may enter the tumor through leaky vasculature and persist, in part, because of reduced lymph clearance [18] in tumors by a phenomenon referred to as the enhanced permeability and retention effect (EPR) [19]. The efficiency of the EPR depends on tumor size, tumor type, and tumor heterogeneity, among other factors. The efficiency of the EPR is also critically dependent on the size of the therapeutic being targeted. As described by Maeda, localization of substances via the EPR is functionally operational over the MW range 40 kDa–800 kDa, which for globular proteins corresponds to minimal radii from 2.3 to 6.1 nm [20]. The preferred dimensions for the localization of proteins in tumor tissue via the EPR surprisingly revealed a minimum at 25 kDa with enhanced uptake for proteins larger or smaller – although smaller peptides required active targeting for retention. In contrast, liposomes did not benefit from active targeting [20, 21]. A variety of NPs have been shown to localize in tumor tissue via the EPR including multiwalled carbon nanotube (MWNT), single-walled carbon nanotube (SWNT) [22, 23], and liposomes [24], as well as viral NPs [25]. NPs may differ considerably in density, and other features from globular proteins and NPs several hundred nanometers in a single dimension have been reported to localize to tumor tissue via the EPR. To our knowledge, the relative efficiency of tumor localization via the EPR for various NPs has not been systematically investigated in any tumor model. An interesting variant of passive targeting via the EPR was recently described in which gold nanorods were delivered to tumor tissue via the EPR and used to heat the tumor upon laser irradiation. The procedure was followed by delivery of the anticancer agent ADHGM to cancer cells through recognition of GRP78 that was upregulated on prostate cancer cells in response to the increased temperature [26].

2.2 Active targeting

In principle, any ligand that displays preferential binding toward malignant relative to nonmalignant cells or that results in selective activation proximal to malignant cells [27, 28] can be used to actively target malignant cells. In this regard, growth factor receptors such as epidermal growth factor receptor (EGFR) [29], transferrin [30–33], death receptor (DR) complexes (e.g., DR5 [34, 35]), and folate ligand [36–40] as well as tumor-specific antigens (e.g., PSMA [41, 42]) have all been utilized to localize NPs to malignant cells via active targeting. A variety of chemical and biological molecules have been used to direct NPs to malignant cells expressing the molecular target receptor including monoclonal antibodies [43], small molecules, and nucleic acid aptamers [44, 45]. Factors that contribute to one type of targeting molecule being preferentially utilized include molecular weight (MW), targeting affinity, valency, and biocompatibility. Although active targeting is conceptually straightforward, this type of targeting does not uniformly enhance tumor localization. For example, monoclonal antibody (mAb) targeting was found in some instances not to enhance tumor localization [46]. Further, active targeting may impact other variables, such as time in circulation, and these indirect effects may confound the effects of direct targeting. Using variable amounts of targeting ligand, it was shown that active targeting of NPs affects cellular uptake within a tumor, but not the targeting to the tumor itself [30]. Thus, active targeting remains an important strategy for NP localization; however, caution must be exercised in attributing the biological effects observed to active targeting.

2.3 Minimizing MPS uptake

The accumulation of NPs in tumor tissues requires prolonged time in circulation and avoidance of clearance through uptake by the reticuloendothelial system (RES) (a.k.a. MPS [47]). Coating of NPs with polyethylene glycol (PEG) or other amphipathic agents reduces the affinity of proteins involved in the opsonization of NPs and, thus, reduces MPS uptake [48]. PEGylation reduced MPS uptake of quantum dots (QDs) up to ninefold, while peptide derivatization had a lesser effect [49]. Dai and coworkers showed that using 90 kDa amphiphilic poly(maleic anhydride-alt-1-octadecene)-methoxy poly(ethylene glycol) [C18-PMH-mPEG], they were able to get 30% of the administered dose of modified SWNT localized in tumor tissue [22, 23]. A recent study evaluated the effects of surface modification of gold nanoparticles (GNPs) on the interaction with blood components including NP biodistribution [50]. GNPs are internalized by monocytes regardless of surface modification. Enhanced tumor accumulation correlated with enhanced circulation and was found to be surface-dependent with fresh, rather than lyophilized PEG, enhancing time in circulation. The effects of surface charge on cell uptake and biodistribution of PEG- oligocholic acid micelles were systematically evaluated [51]. A slight negative charge was found to maximize tumor uptake and minimize uptake by MPS cells of the liver. Surface modification to reduce MPS uptake continues to be an important strategy for developing NPs with improved therapeutic activity. For example, low MW chitosan has been developed as an alternative to PEGylation that may allow for retention of specific molecular interactions that are masked by PEG [52].

3 NP-mediated cancer imaging

NPs may be highly useful for imaging applications [53] because of the high surface area-to-volume ratio (relative to larger particles) as well as having the potential for numerous sites for chemical modification that may be used to amplify imaging sensitivity [53]. While the avoidance of macrophage uptake is important for NP-mediated effects in many instances, the propensity of NPs to undergo macrophage-mediated phagocytosis may be beneficial for imaging applications. Superparamagnetic iron oxide NPs (IONPs) have been used for MR imaging of lymph nodes following macrophage uptake, which may be beneficial for detecting metastatic disease [54, 55]. The poor lymphatic drainage of tumors that contributes to accumulation of NPs for drug-delivery applications may also be used to image tumors with IONPs [56]. IONPs have also been conjugated to the amino-terminal fragment of urokinase plasminogen activator to specifically image breast cancer [57], while conjugation with an antibody to EGFR was used for imaging brain tumors [58]. Generalized chemical methods for developing surface-modified IONP for cancer imaging are being developed [59]. Recently, a new approach for in vivo assembly of NPs with imaging agents was described [60].

Several different types of NP have been conjugated with chelates of paramagnetic Gd³⁺ to enhance MR contrast including dendrimers, micelles, and cNTs [61]. In principle, highly specific imaging of small numbers of malignant cells could be achieved by conjugating a targeting agent, such as a mAb, with Gd³⁺-chelates to affect MR relaxivity or conjugating with other imaging probes. In practice, sensitivity is a problematic issue of imaging research. One potential approach is to amplify the signal in the area of interest by delivering a suitable enzyme. For example, horseradish peroxidase has been delivered to xenograft tumors via conjugation to a tumor-specific mAb, and this has been used to oligomerize MR-specific ligands to achieve an enhanced signal for tumor detection and imaging [62]. GNPs have also been used for enhancing contrast in X-ray images providing advantages relative to triiodobenzene [63]. In addition to enhancing contrast for improved imaging, GNPs affect X-ray scatter and can be used to localize radiation and improve treatment outcomes [64, 65].

In principle, NPs can be used for both imaging and treatment applications [66]. For example, TiO₂ NPs may be used both to enhance CT (computed tomography) image contrast and as sensitizers for photodynamic therapy [67]. Magnetic NPs can be used for both improved MR imaging and hyperthermia applications for advanced cancer treatment [68]. The α_vβ₃ integrin-specific peptide motif RGD may be used to direct IONPs to malignant cells for both enhancing contrast as well as hyperthermia-based therapy [69]. IONPs can be conjugated with methotrexate [70], paclitaxel (PTX) [71], or other anticancer drugs [72] for theranostic (therapeutic+diagnostic) applications. Gold NPs, quantum dots, and cNTs have also been modified and utilized for potential theranostic applications [69].

4 NP-mediated cancer treatment

NPs that are being used for, or developed for, cancer treatment are generally not inherently cytotoxic. Thus, NPs must alter the chemical and/or physical environment specifically in the region proximal to the cancer cell in order to exert cytotoxicity. As mentioned in the preceding sections, NPs are targeted to malignant cells specifically via passive targeting via the EPR and/or active targeting, frequently based upon specific molecular recognition events such as EGF/EGFR interactions. Once localized to the tumor, NPs evoke a cytotoxic response in cancer cells generally using one of three modalities: (1) drug release [73], (2) hyperthermia or thermal ablation [74], and (3) reactive oxygen species (ROS)-mediated killing [75]. These modalities can be applied independently or may be utilized together in a multimodality approach for cancer treatment. The advantages relative to non-NP-mediated approaches for ablation are that NPs may mediate extremely localized effects that are based on molecular recognition events at a cellular level. Thus, by directing NPs to specific cells (e.g., malignant cells), one can enhance eradication of neoplastic tissue while limiting damage to proximal or even adjacent normal cells. This sort of approach is particularly valuable for highly infiltrative malignancies, such as glioblastoma multiforme (GBM), where malignant cells cannot be positionally distinguished from nonmalignant cells.

4.1 NP-mediated drug release

NP-mediated drug delivery is based upon the premise that it is, for the most part, no more difficult to kill a cancer cell than any other nonmalignant cells. Conventional cytotoxic agents, such as doxorubicin (DOX), are highly cytotoxic to cancer cells but are, unfortunately, highly cytotoxic to nonmalignant cells as well – particularly rapidly dividing cells in the gastrointestinal tract and bone marrow. NP-mediated delivery of conventional cytotoxic drugs allows for control over drug cytotoxicity based upon the biodistribution profile for the NP rather than for the free drug [76, 77]. NP-mediated drug delivery also reduces the excretion rate for low MW cytotoxic drugs providing an increased opportunity to remain in the circulation and accumulate in the targeted region. A successful example of nanotechnology-mediated drug delivery is the liposome-mediated delivery of DOX (e.g., Doxil) [78] that has substantially reduced cardiotoxicity [79] relative to free DOX. The albumin-conjugated PTX NP (Abraxane) demonstrated promising efficacy in breast cancer as well as ovarian cancer and is approved by the FDA [80, 81]. The platform of nanotechnology addressed the hydrophobicity-related issue of PTX and helped to prepare a toxic solvent (cremphor)-free formulation reducing the overall toxicity of the therapeutic [80]. A number of recent studies have also proposed novel approaches for improved drug-delivery using NPs. Our laboratory has shown that creating a nano-sized DNA polymer results in enhanced antileukemic activity relative to low MW drugs [82].

4.2 Controlling NP-mediated drug release

The use of NPs for drug delivery requires release of drug at the tumor site or into malignant cells upon internalization. Thus, strategies to enhance drug release at the tumor site are an important component of NP design strategies for theranostic applications. One of the potential problems with current drug delivery methods is that drug is only slowly released from the NP following localization to tumor tissue via the EPR. This slow release may result in lower free-drug levels that are insufficient to exert a biological, e.g., cytotoxic response [73]. Thermally labile liposomes were developed that expedite drug delivery following tumor localization via the EPR, a strategy that is moving forward into clinical trials [73].

4.3 Clinical candidates for NP-mediated drug delivery

The fundamental features important for successful implementation of NPs as therapeutic agents including passive and active targeting and MPS avoidance have been developed to the extent that NP-based therapeutic candidates beyond liposomes are entering clinical trials and displaying drug release and toxicity profiles demonstrating significant improvements relative to conventional chemotherapy. A particular instance of a NP that combines passive targeting via the EPR with active targeting as well as with evasion of immune cells is BIND-014, which recently entered clinical trials [41]. BIND-014 uses the RNA aptamer A10-03 to localize the NP to prostate cancer cells and releases docetaxel chemotherapy. PEG is used to minimize the uptake of NP by the MPS. Besides use of NP for drug delivery, imaging-based NPs are also entering clinical trials such as [¹⁸F]-FAC family of PET-imaging agents that are being tested for estimation of chemotherapies such as gemcitabine, cytarabine, and fludarabine uptake [83, 84]. Another significantly promising example are NPs containing magnetic resonance imaging (MRI) contrast agents targeted to the α_vβ₃-intregrin found on the surface of the newly developing blood vessels associated with early tumor development [85, 86]. A viral nanoparticle (VPN) has been developed for gene therapy against leukemia [87]. Cyclodextrin-based NP that safely encapsulates a small-interfering RNA (siRNA) agent capable of shutting down a key enzyme in cancer cells is also under clinical trials [88–90]. Cyclodextrin-conjugated camptothecin polymeric NP is in currently under clinical trial [91]. In a collaborative study between Harvard Medical School and MIT, a clinical study is under process to determine the potential of a novel class of superparamagnetic NPs to identify circulating premetastatic cells [92].

4.4 Thermal ablative approaches to cancer treatment

Locally ablative approaches [93] including radiofrequency ablation (RFA) [94, 95], laser-induced thermotherapy (LITT) [96], and microwave ablation [97] are widely used for treatment of metastatic disease [98], chiefly to the lung [99] and liver [100] that originate from diverse primary tumors. These currently implemented thermal ablative approaches do not utilize NPs, and thus, implementation is based on macroscopic detection of metastatic lesions rather than on specific molecular recognition as is becoming increasingly possible using NP-mediated ablative approaches. Radiologic guidance can improve tumor specificity [101, 102] increasing the efficacy of cancer therapy. It is important to note that micrometastatic disease, particularly at sites distant from the primary tumor, is an extremely poor prognostic indicator (Figure 2). Thus, the application of nanotechnology approaches for eradicating micrometastatic disease represents one of the most important objectives for using nanotechnology for cancer treatment. Although not yet specific on a molecular level, current thermal-ablative approaches do have a high demonstrated success rate with up to 97% positive response using RFA and 98% using LITT for treatment of breast metastases [103] and colorectal cancer metastases [104]. Cryoablation alternatively uses localized low temperatures to freeze and kill neoplastic tissue [105]. Our laboratory demonstrated that DNA-encased MWNTs had the capacity to thermally eradicate prostate cancer xenografts [74] in nude mice model upon near-infrared(NIR) radiation, without causing significant damage to the adjacent tissue. DNA enhanced the dispersion of the MWNTs, which as with other NTs, are excited by tissue-penetrating NIR radiation. The use of double-strand DNA (dsDNA)-complexed SWNTs with conjugation to a mAb for selective delivery and localized thermal ablation was recently described [106, 107] as potential cancer therapeutics. Focal ablative therapy is being explored as an alternative to surgery and radiation therapy for the treatment of localized prostate cancer [108]. It is important to note that in addition to any direct thermal ablative effect mediated by NPs, ablative therapies also modulate the immune response, and this will affect the overall antitumor response [109].

Figure 2.

Comparison of short- and long-term effects of treatment with conventional agents (top panels) and NPs that use both active and passive targeting of malignant cells (bottom panels). Conventional approaches are equally effective in the short term; however, micro-metastases remain and repopulate the tumor in the long term. Targeted NPs destroy micrometastases resulting in long-term therapeutic benefit.

4.5 Nanotechnology and photodynamic therapy

The cytotoxic effects of photosensitizing porphyrins in conjunction with light exposure are well documented, and photodynamic therapy (PDT) is widely used for treating bladder cancer [110], esophageal cancer [111], as well as for other malignancies and other neoplastic conditions such as macular degeneration [112]. NP-mediated delivery of photosensitizing porphyrins [113] would be expected to confer several of the same advantages that are associated with NP-mediated delivery of cytotoxic drugs including increased local intratumoral concentrations resulting from the enhanced permeability and retention (EPR) effect [12] and reduced systemic toxicities and, in the case of photoactive compounds, reduced light sensitivity [114]. Alternatively, locally administered NPs composed, in part, of photosensitizing porphyrins would be expected to be retained in the targeted tissue allowing multiple exposures to light with a single administered dose.

4.6 Nanoparticle-mediated gene therapy

Although it has been known for decades that DNA is the molecular basis of life that carries information from generation to generation, until nanotechnology started using DNA for the detection of macromolecules or to produce biochips, other potentials of this biomolecule has not been realized. The cellular role of DNA is relatively limited, perhaps, because of the restrictions imposed by structure and bonding between complementary strands. Apart from these cellular roles, nanotechnology is now discovering many more hidden potentials of DNA. By exploiting its amphipathic property, single-stranded DNA (ssDNA) sequences could be used to solubilize hydrophobic NPs like carbon nanotubes (cNTs) to make it suitable for in vivo use. DNA sequences have the ability to process information in biochemical assays. Its structure and self-assembling property made it an ideal scaffolding material to arrange NPs in biochip and biosensor production.

Antisense gene therapy is a potentially powerful tool for both biomedical researches as well as for clinical treatments of various ailments, including cancer. Although the potential of antisense gene therapy was recognized decades ago, their development into viable therapeutics has faced challenges with regard to low transfection efficiency, DNAse degradation, entry into diverse cell types, and toxicity of the transfecting agents. In the last few years, several researchers demonstrated the potential of augmenting gene therapy with the help of nanotechnology [87, 88, 90, 115, 116] addressing a majority of these issues and successfully translated into clinical trials.

4.7 Multimodality NPs for cancer treatment

Tumors are heterogeneous in nature, consisting of multiple cell types and with complex interplay between the cellular components contributing to make treatment challenging. One of the potential advantages of nanotechnology is the capacity to deliver and/or utilize more than a single therapeutic modality for treatment. Our laboratory is investigating a novel multimodality NP that displayed strong antitumor activity through light-mediated ROS generation with release of DNA (Ghosh et al., in preparation). An example of a nanomaterial that had been used for multimodality applications, including drug-delivery and thermal ablation, are cNTs [117]. Heat alone is unlikely to be an ideal modality for inducing tumor cell death as heat can be dissipated by blood vessels. Heat can also enhance chemotherapeutic efficacy (hyperthermia), and heat-mediated chemotherapy release may augment or enhance direct thermal ablation. Nutritional deprivation, hypoxia, and acidic pH have all been demonstrated to sensitize tumor cells to hyperthermia [118, 119].

Chemosensitization resulting from hyperthermia can enhance therapeutic efficacy of chemotherapy, and multi-modality NPs can be used for both drug delivery as well as stimulation of hyperthermia. A portion of the hormone FGF was used to direct gold NPs to U2OS cancer cells that had been transfected with the fibroblast growth factor receptor (FGFR), and it was demonstrated that cell death could be induced upon exposure to NIR irradiation [120]. Gold nanospheres were recently loaded with DOX and targeted to EphB4-expressing tumors using a peptide identified using phage display [121]. Hyperthermia was stimulated by NIR irradiation; however, other approaches including use of alternating magnetic fields in conjunction with IONPs [122] are being evaluated in preclinical as well as clinical studies, and the use of high-intensity focused ultrasound (HIFU) for hyperthermia in conjunction with thermo-sensitive liposomes (TSL) was recently described [123]. Temperature-triggered release of the drug from liposomes is expected to enhance local drug concentrations in the tumor-enhancing treatment efficacy without increasing systemic toxicity. While temperatures above 42°C may shut down blood flow, temperatures in the 41–42°C range can markedly enhance the effects of chemo therapy and radiation treatment. For example, approximately 30% less radiation is required to kill cells heated to 42°C relative to physiological temperature [124], although it is technically difficult to maintain tissue temperatures in a controlled fashion above physiological temperature. MR is valuable in temperature mapping, and MR-HIFU systems can be used to locally control temperatures.

5 NP-related toxicity

One of the potential risks of using nanomaterials for cancer therapy as well as for human health, in general, is the potential for toxicity [68, 75, 125]. Nanomaterials are diverse in chemical composition, charge, and even to some degree size, and thus, general statements concerning toxicity are likely not possible. Some of the major concerns are that NPs may be carcinogenic by, for example, causing increased ROS production and leading to DNA mutations. NP exposure is also associated with asthma, bronchitis, Alzheimer’s disease, and Parkinson’s disease. A variety of vascular-related events such as blood clots are associated with NPs that enter the circulatory system. Further research is required to delineate real risks associated with NP use and determining to what extent potential benefits outweigh these risks.

6 Summary and future perspective

Nanotechnology is playing an increasingly important role in cancer diagnosis and treatment. The size regime of NPs is small compared to cells and cellular organelles permitting NPs to interact with specific features of cells and allowing for tumor cell localization through active targeting [76, 126]. The size regime of NPs is also appropriate for passive targeting to tumor tissue via the EPR [77]. Thus, nano-sized materials have particular advantages for cancer treatment with distinct features relative to low molecular weight drugs. These properties are being effectively exploited for improved delivery of chemotherapeutic drugs [78] resulting in both enhanced anticancer activity and reduced systemic toxicity.

The chemical diversity of NPs allows for interactions with magnetic fields [127], NIR irradiation [128], and other external fields to provide a conduit for highly specific interactions between external fields with tumor tissue and potentially with individual malignant cells in vivo. The diverse material composition of NPs also permits perturbation of external fields providing enhanced contrast for imaging applications [129]. The unparalleled specificity of coupling between external fields and malignant cells in the context of normal tissue provided by appropriate NPs is expected to lead to more accurate and earlier diagnoses and improved treatment outcomes. One concern potentially limiting the applicability of some NPs for cancer treatment is the toxicity [79] of nanomaterials that requires further investigation. Nonetheless, improved cancer treatments using nanotechnology will continue to be developed and result in improved treatment outcomes.

Abbreviations

cNT

carbon nanotube

CT

computed tomography

DOX

doxorubicin

DR

death receptor

dsDNA

double-strand DNA

EGFR

epidermal growth factor receptor

EPR

enhanced permeability and retention effect

FGFR

fibroblast growth factor receptor

GBM

glioblastoma multiforme

GNP

gold nanoparticle

HIFU

high-intensity focused ultrasound

HPV

human papilloma virus

IONP

iron oxide nanoparticle

i.v.

intravenous

LITT

laser-induced thermo-therapy

mAb

monoclonal antibody

MPS

macrophage phagocytic system

MR

magnetic resonance

MW

molecular weight

MWNT

multi-walled carbon nanotube

NIR

near infrared

NP

nanoparticle

PEG

polyethylene glycol

PL

phospholipid

PTX

paclitaxel

RES

reticuloendothelial system

RF

radiofrequency

RFA

radiofrequency ablation

ROS

reactive oxygen species

ssDNA

single-stranded DNA

SWNT

single-walled carbon nanotube

TSL

thermosensitive liposome

Biography

Supratim Ghosh (left) received BSc and MSc degrees from the University of Calcutta and recently received his PhD from the Molecular Genetics program at WFSM performing research focused on improved cancer treatment using nanotechnology under the supervision of Dr. Gmeiner.

William Gmeiner (right) was awarded a Bachelor’s degree with honors from the University of Chicago and a PhD in Chemistry from the University of Utah and was an Alberta Heritage Medical Research Fellow. Dr. Gmeiner is currently Professor of Cancer Biology at Wake Forest School of Medicine. He has published more than 70 peer-reviewed articles in chemistry, cancer biology, and nanomedicine and recently was granted a SPARK award for innovative new research at WFSM.