A Carrier-Free, Co-assembled Nanoplatform for Synergistic Photothermal Therapy: Integrating High-Efficiency BODIPY with Heat Shock Protein Inhibitors

Abstract

The simultaneous delivery of boron-dipyrromethene (BODIPY) photosensitizers and heat shock proteins (HSPs) inhibitors to tumor sites can enhance the therapeutic efficacy of photothermal therapy (PTT). Current strategies mainly rely on physical encapsulation into nanocarriers or chemical conjugation onto polymer backbones for the co-delivery of BODIPY and HSP inhibitors. However, these approaches are hampered by drug leakage, reproducibility, or synthetic polydispersity. Herein, we report a carrier-free, co-assembled, and self-delivery nanoplatform to overcome these limitations. An amphiphilic BODIPY derivative (BODIPY-OEG) was synthesized and co-assembled with HSP inhibitors quercetin (Q), yielding nanoparticles (B@Q) with high photothermal conversion efficiency. The resulting B@Q nanoparticles not only possessed favorable photothermal performance in vitro but also had been demonstrated to possess potent antitumor capabilities by inhibiting the expression of HSPs in tumor cells. In vivo, B@Q demonstrated potent antitumor activity by suppressing subcutaneous tumor growth and lung metastasis, while also eliciting a potent systemic immune response, demonstrating its excellent antitumor efficacy. This work proposes a simple and precise co-assembly strategy to construct carrier-free, multifunctional nanotherapeutics, which opens avenues for the concept of self-delivered synergistic PTT agents.