Gold Nanoparticle-Carrying T Cells for the Combined Immuno-Photothermal Therapy.

ABSTRACT

Cancer immunotherapy is a promising therapy to treat cancer patients with minimal toxicity, but only a small fraction of patients responded to it as a monotherapy. In this study, a strategy to boost therapeutic efficacy by combining an immunotherapy based on ex vivo expanded tumor-reactive T cells is devised, or adoptive cell therapy (ACT), with photothermal therapy (PTT). Smart gold nanoparticles (sAuNPs), which aggregates to form gold nanoclusters in the cells, are loaded into T cells, and their photothermal effects within T cells are confirmed. When transferred into tumor-bearing mice, large number of sAuNP-carrying T cells successfully infiltrate into tumor tissues and exert anti-tumor activity to suspend tumor growth, but over time tumor cells evade and regrow. Of note, ≈20% of injected doses of sAuNPs are deposited in tumor tissues, suggesting T cells are an efficient nanoparticle tumor delivery vehicle. When T cells no longer control tumor growth, PTT is performed to further eliminate tumors. In this manner, ACT and PTT are temporally coupled, and the combined immuno-photothermal treatment demonstrated significantly greater therapeutic efficacy than the monotherapy.