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.
Highlights
Gold nanoparticles (AuNPs) have been successfully used to enable photothermal therapy (PTT) for the treatment of cancer in small animal studies [1,2,3,4,5], and has recently moved towards clinical application [6]
T cells from three different human donors were first cultured with concentrations of gold nanoparticles (AuNPs) ranging from 0.05 to 0.5 nM for a period of 24 h to evaluate for variability in gold nanoparticle loading due to differences in T cells from different donors (Figure 1c)
At 24 h, the 0.5 and 1 nM groups have similar gold content, suggesting that there is a maximum amount of AuNPs that can be internalized by T cells
Summary
Gold nanoparticles (AuNPs) have been successfully used to enable photothermal therapy (PTT) for the treatment of cancer in small animal studies [1,2,3,4,5], and has recently moved towards clinical application [6]. Choi et al [17] recently demonstrated that macrophages could be used as a cellular delivery vehicle to deposit AuNPs in tumors and hypoxic tumor tissues, facilitating delivery through active cellular migration and extravasation in response to chemotactic factors produced by malignant cells. These encouraging results suggested that other immune cells might be used as cellular delivery vehicles. This tumor-tropic property permits their use as cellular vehicles for the delivery of molecular therapeutics [18,19,20,21]
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