T cells enhance gold nanoparticle delivery to tumors in vivo

Abstract

Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

Polyester-idarubicin nanoparticles and a polymer-photosensitizer complex as potential drug formulations for cell-mediated drug delivery

“…For the treatment of experimentally induced tumors mainly lymphokine activated killer (LAK) cells, macrophages, mesenchymal stem cells, and erythrocytes were utilized as drug carriers (Batrakova et al, 2011). Delivered therapeutics include ricin (Cerundolo et al, 1987;Zanovello et al, 1992), doxorubicin and derivatives (Mandruzzato et al, 1994;Zocchi et al, 1989), liposomal 5-fluorouracil (Ikehara et al, 2006), nanoparticulate gold (Kennedy et al, 2011) as well as magnetic nanoparticles (Basel et al, 2012). In addition, genetically modified cells expressing immunotoxins, apoptosis-inducing proteins, and immunomodulating cytokines were tested in cell culture and animal experiments (Pereboeva and Curiel, 2004).…”

Gamma irradiation of ocular melanoma and lymphoma cells in the presence of gold nanoparticles: in vitro study

“…Previously, it has been shown that loading gold NPs into prostate, skin melanoma, and liver tumors, which are later exposed to irradiation, results in greater dose absorption within the tumor than the surrounding tissues 15, 16, 17, 18…”

The Combination of Laser Therapy and Metal Nanoparticles in Cancer Treatment Originated From Epithelial Tissues: A Literature Review

“…Transformation of nanoparticles can be done in a systemic way (through intravenous injection). 9,10 Many studies have been done in this field.…”

“…On the other side near infrared (NIR) radiation is an interesting energy source as human blood and body tissues have the minimum absorption in this wavelength, thus deeper tissues can be reached. 9 The unique features of lasers such as photo-thermal properties and the extremely small size of nanoparticles (which creates new physical effects that are mainly a result of domination of the quantum properties in contrast to classical properties), provide an interesting combined therapeutic effect. Thermal therapy procures a fast recovery, shorter hospital stay, less complications and is easy to perform.…”