Received Date: November 12, 2012; Accepted Date: November 14, 2012; Published Date: November 16, 2012
Citation: Ramos J, Taylor D, Rege K (2012) Gold Nanoparticle Mediated Photo- Chemotherapy. J Nanomed Nanotechol 3:e125. doi:10.4172/2157-7439.1000e125
Copyright: © 2012 Ramos J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Photothermal therapy; Hyperthermia; Gold nanoparticles; Drug delivery
Surgery, radiation, and chemotherapy are the most common methods of combating cancer diseases. Despite several successes in treatment, it is necessary to develop better strategies that are capable of destroying cancer cells while limiting off-target damage of nonmalignant cells. Nanotechnology offers exciting options for the siteselective delivery of current treatments to cancer cells . Nanoparticle (NP)-based therapeutics involve the ability to engineer novel nanoscale platforms that can combine different treatment and in some cases, imaging modalities for a more aggressive, yet safer approach for cancer cell ablation. Whereas free chemotherapeutic drugs may diffuse nonspecifically in tissues, NP-based delivery vehicles can localize into tumors due to the enhanced permeation and retention (EPR) effect. In addition, modification of NPs with appropriate ligands facilitates cancer cell targeting (i.e., molecules that bind to specific receptors overexpressed on cancer cells). Consequently, several classes of nanocarriers have been engineered for delivery of a wide range of cancer chemotherapeutics . Of these systems, those based on gold NPs have received increasing attention for applications in drug delivery and imaging . Gold particles exhibit unique optical properties when reduced to the nanoscale, and engineered to certain geometries. Surface plasmon resonance of gold nanoparticles allows them to strongly absorb and scatter incident light as well as convert resonant energy to heat. Several classes of gold nanoparticles have been engineered such that their plasmon resonance is tuned to near infrared (NIR) wavelengths, which allows them to absorb and convert this energy to heat leading to hyperthermic temperatures of surrounding media [4,5]. As a result, gold nanoparticles (GNPs) have received increased attention for localized administration of hyperthermia for cancer cells ablation, and this approach is currently in early clinical trials . While hyperthermic treatments represent a promising approach for cancer therapy, they suffer from non-uniform heat distribution especially in areas located near large blood vessels, where heat can dissipate rapidly to circulating blood . Additionally, hyperthermia is limited by cellular thermotolerance, whereby cells treated with low intensity repeated hyperthermic treatments are able to maintain viability due to an array of cell survival responses [8,9]. Combinatorial/synergistic treatments for cancer therapy can be developed by engineering NPbased systems that can be employed for simultaneously engendering hyperthermia and delivering chemotherapeutic drugs for enhanced ablation of cancer cells. In addition, hyperthermia increases tumor tissue perfusion, allowing easier absorption of chemotherapeutic drugs through cell membranes, leading to greater efficacies between the two treatments (i.e., hyperthermia and the delivered chemotherapeutic drug). Indeed, hyperthermia has been shown to reduce tumor resistance to various chemotherapeutic drugs including doxorubicin, cisplatin, bleomycin, nitrosoureas, and cyclophosphamide [10-12]. The ability to combine drug delivery and photothermal therapy on GNPbased delivery platforms has potential for higher efficacies of cancer cell ablation. This GNP-based photochemotherapy approach is a versatile strategy in which, drugs that kill cancer cells by diverse mechanisms can be employed in combination with photothermal ablation. Several studies have demonstrated the ability of different GNP-based platforms for the delivery of cancer cell-targeted chemotherapeutics, and the simultaneous NIR light-based induction of hyperthermia. For example, the antineoplastic drug doxorubicin, has been loaded into hollow gold nanospheres (HAuNS) [7,13], hollow gold nanoshells , and poly(ethylene glycol)-poly(lactic-co-glycolicacid)-Au half-shell nanoparticles (DOX-PLGA-Au H-S NPs) [15,16] for dual delivery of the drug and simultaneous application of NIR photothermal therapy. Similarly, gold nanoshells on silica nanorattles (GSNs)  have been investigated for delivery of the anti-cancer therapeutic docetaxel and simultaneous application of NIR photothermal therapy. Our group has investigated elastin-like polypeptide (ELP)-gold nanorod nanocomposites for dual delivery of the anti-cancer drug, 17-AAG simultaneously with NIR photothermal therapy . Interestingly, the drugs used in these studies, ablate cancer cells via different mechanisms; doxorubicin is a DNA intercalating agent that inhibits DNA synthesis , docetaxel is a microtubule stabilizing agent that limits mitosis , and 17-AAG is an inhibitor of heat shock protein 90 (HSP90) which is a prosurvival protein that allows cells to resist hyperthermia . In both, in vitro and in vivo studies, the combined chemotherapeutic drug and photothermal treatments using drug-loaded GNP platforms exhibited improved, and in some cases, complete cancer cell/tumor destruction, when compared to the GNP platform or drug alone. In addition, NIR treatment also aided controlled release of the loaded drug from the GNPs. Although GNP-induced hyperthermia is a promising approach for cancer cell ablation, one major limitation of administering this treatment is the depth of penetration of NIR light.
Currently, the most advanced NIR laser systems are limited to a penetration depth in soft tissue of up to approximately 2 cm . This limits the application of hyperthermia treatments, including those based on GNPs, to topical or near-surface applications. However, due to this depth limitation, alternative techniques have been pursed in order to reach increased depths. Using minimally invasive interventional techniques, fibres inserted directly into tumors/tissues have been investigated for administration of laser-based hyperthermic treatment for primary and metastatic liver cancer [23-25] as well as in lung metastases . In addition, delivery of NP-based therapies for combination photo-chemotherapy can also be applied to inoperable, advanced diseases, as well as in combination with surgery . As studies continue to emerge for the use of GNP platforms for combined drug delivery and photothermal therapy, their potential for increased efficacies of cancer cell eradication will continue to be highlighted. It will also become increasingly important to design and investigate mechanism-based combination treatments that overcome cancer cell resistance. The integration of emerging imaging techniques that allow for in vitro and in vivo imaging of GNPs including NIR-induced twophoton luminescence [27,28], photoacoustic imaging  and dark field imaging  can allow for image-guided combination treatments to tumors. It is increasingly evident that multifunctional GNPs have tremendous potential as emerging theranostic platforms for simultaneous administration of hyperthermia and chemotherapeutic drugs, together with imaging, for applications in cancer treatment.