An engineered-exosome disguised multifunctional nanoplatform for enhanced chemo-photothermal therapy of triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) with high postoperative recurrence rate and aggressive invasiveness remains a significant threat to women. Here, we developed an engineered-exosome disguised multifunctional nanoplatform (IG Exo-Lipo) utilizing engineered exosomes mixed with liposomes as carriers, encapsulating both IR780 and gambogic acid prodrug (MPEG-TK-GA), to enhance the efficacy of chemo-photothermal therapy for the treatment of TNBC. The disguise of SIRPα gene engineered-exosome endowed IG Exo-Lipo with low immunogenicity, long circulation time, and innate targeting capability. Upon entering tumor cells, the loaded IR780 in the IG Exo-Lipo mediated low-temperature photothermal therapy (PTT) and generated reactive oxygen species (ROS) under NIR light irradiation. Immediately, gambogic acid was released on-demand by MEPG-TK-GA cleaving under the stimulation of ROS, allowing for low-dose chemotherapy while simultaneously enhancing low-temperature PTT through the downregulation of heat shock protein 90. In vitro and in vivo antitumor evaluations indicated that IG Exo-Lipo improved therapeutic efficacy significantly by synergistic enhancement of chemo-photothermal therapy. Overall, the engineered-exosome disguised multifunctional nanoplatform enabled an enhanced chemo-photothermal treatment of TNBC, showing promising clinical application potential.

Keywords

• Gene engineered-exosome
• ROS response
• Low-temperature PTT
• Low-dose chemotherapy
• Synergistic therapy