Nanoscale Gambogic Acid Liposomes for NIR-II Photoacoustic Imaging and Photothermal-Chemo Tumor Therapy

Photothermal therapy (PTT) has attracted widespread interest due to its precise spatiotemporal selectivity and minimal noninvasiveness. However, it is still limited by the depth of light penetration, thermoresistance of tumors, and limitations of monotherapeutic modalities. In this study, we synthesized an organometallic photosensitizer (NiPTZ) with the capability of photothermal conversion in the second near-infrared (NIR-II) range, making it a promising candidate for photoacoustic imaging (PAI)-guided PTT. To mitigate the impact of excessive heat shock proteins (HSPs) expression caused by thermal damage on PTT efficacy, we developed nanoscale thermosensitive (gambogic acid) GA-liposomes Lip(NiPTZ-GA) by self-assembling PEGylated gambogic acid (GA, HSP90 inhibitor), NiPTZ, DPPC, and DSPE–PEG2000. Upon the NIR-II light irradiation, Lip(NiPTZ-GA) generated high temperatures and underwent dissociation to release NiPTZ, enabling efficient PTT and PAI. GA-PEG suppressed heat-induced overexpression of HSP90 successfully, while achieving synergistic chemotherapy. Downregulation of HSP90 could reduce the thermoresistance of tumors and enhance the therapeutic efficiency of PTT. This study presents an innovative multifunctional liposome platform for NIR-II PAI-guided enhanced PTT combined with chemotherapy.