Gold-caged copolymer nanoparticles as multimodal synergistic photodynamic/photothermal/chemotherapy platform against lethality androgen-resistant prostate cancer

Abstract

Given that there is no effective treatment method for lethality androgen-resistant prostate cancers (ARPC), herein we report a multifunctional gold-caged nanoparticle (PTX-PP@Au NPs) against ARPC through integrating functional organic/inorganic materials to exploit the superiors of gold particles such as photothermal effects (PTT), generating reactive oxygen species (photodynamic effects, PDT), carrying chemotherapeutic agents (chemotherapy effects, CT), and inhibiting ion channel. This synergistic PTT/PDT/CT platform consists of three components: i) the Pluronic-polyethylenimine assembling into micelles to encapsulate drugs and providing reduction sites for gold cage formation through a "green" method, ii) the gold cage with surface plasmon resonance peak at near-infrared (NIR) region in a broad window qualifying the PTT/PDT potentiality, iii) a chemotherapeutic agent paclitaxel (PTX) arresting the tumor cell cycle. As demonstrated, the system has remarkable performance on controlling drug release, blocking TRPV6 cation channel, enhancing cell cycle arrest, elevating temperature and generating ROS, thus improving cellular toxicity along with apoptosis, enhancing tumor targeting, and achieving the therapy to ARPC with low toxicity on liver function and minimal side effects to normal organs. Notably, both PTT and PDT effect are generated under single irradiation situation because of the broad absorbance window, along with limited skin damages. As a specific synergistic platform creatively integrating multiple treatment protocols with negative toxicity, PTX-PP@Au NPs provide a facile, effective, and broadly applicable strategy to deadly ARPC.

Keywords: Androgen-resistant prostate cancers; Gold cage; Photothermal-photodynamic-chemotherapy; Single irradiation; TRPV6 channel.