NIR-Activated Spatiotemporally Controllable Nanoagent\nfor Achieving Synergistic Gene-Chemo-Photothermal Therapy in Tumor\nAblation

Abstract

A rational combination\nof different therapeutic modalities within\none single nanostructure is promising to enhance the therapeutic response,\nespecially to achieve a synergistic therapeutic efficacy for tumor\ntreatment. Herein, a near-infrared (NIR) photothermally activated\nnanoagent, which could achieve a spatially controllable codelivery\nof different curative molecules and a temporally controlled responsive\nrelease, was designed to perform effective gene-chemo-photothermal\ntherapy of malignant tumors. The nanoagent consisted of a gold nanorod\n(AuNR) functionalized with mPEG, DNA, and small interfering RNA (siRNA).\nWith the aid of aptamer AS1411-mediated recognition and endocytosis,\nthe nanoagents were selectively delivered into cancer cells; subsequently,\nthe photothermal conversion of AuNRs happened while under NIR irradiation,\nwhich successfully achieved an effective photothermal therapy, induced\ndehybridization of DNA duplexes, and simultaneously released doxorubicin\n(DOX) and siRNA. Then, the released siRNA silenced the expression\nof the multidrug resistance associated protein 1 (MRP1), the primary\ncause of the undesirable expelling of DOX in PC-3 cells, yielding\na remarkable improvement in the efficiency of gene-chemo therapy.\nAll of the results of <i>in vitro</i> and <i>in vivo</i> studies revealed that our prepared nanoagents exhibited an excellent\nperformance in synergistic gene-chemo-photothermal therapy and successfully\ninhibited tumor growth. This work provides an interesting concept\nof a nanoscale therapeutic agent in achieving a dramatically enhanced\ntherapeutic ability for tumor ablation, which benefits from\nthe spatiotemporally controllable properties and the synergistic combination\nof chemotherapy, gene therapy, and photothermal therapy in one single\nnanoagent.