Gambogic acid augments black phosphorus quantum dots (BPQDs)-based synergistic chemo-photothermal therapy through downregulating heat shock protein expression

[Display omitted] •BPQDs and GA encapsulated polymeric nanoparticles are fabricated using the SCF technology.•GA promoted the PTT efficiency of BPQDs by hampering the thermoresistance of cells.•PA imaging-guided synergistic PTT-chemotherapy is achieved towards cancer ablation. In an attempt to attain synergistic therapeutic benefits and address various intrinsic limitations of the highly efficient black phosphorus quantum dots (BPQDs), we fabricated poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) triblock copolymer (PLLA-PEG-PLLA)-based nanocomposites co-loaded with BPQDs and gambogic acid (GA) using the supercritical carbon dioxide (SC-CO2) technology to achieve photoacoustic (PA) imaging-guided synergistic chemo-photothermal therapy. On the one hand, BPQDs displayed near-infrared (NIR)-induced hyperthermia through the high photothermal conversion efficiency. On the other hand, the NIR-responsive release of GA facilitated early apoptosis through specific binding to stress-induced overexpression of heat shock protein (HSP)-90 for combating thermoresistant tumor cells. GA significantly promoted the photothermal therapy (PTT) efficiency by enhancing both early and late apoptosis of BPQDs. Moreover, the encapsulation of BPQDs in the polymer significantly improved their chemical as well as photothermal stabilities. Our findings suggested that these nanocomposites fabricated using the eco-friendly supercritical fluid (SCF) technology provided good protection to the biodegradable BPQDs, offering a great potential towards cancer ablation through augmented synergistic effects.