Self-Assembled Chemo/Photothermal Nanoplatform for Enhanced Cancer Therapy: Sensitizing Photothermal Ablation and Reprogramming Inflammatory Microenvironment

Photothermal therapy (PTT) has become a promising method for cancer treatment through photothermal ablation. Nevertheless, its efficacy is often compromised by the upregulation of heat shock proteins (HSPs) and the activation of inflammatory cascades. Herein, this study introduced a well-designed chemo- and photothermal nanoplatform (CI-NPs) by non-covalent self-assembly of curcumin (Cur, a multifunctional small molecule) and IR-1061 (a NIR II photothermal agent), without the help of excipients. The CI-NPs demonstrated uniformity in size, efficient photothermal conversion following 1064 nm irradiation, improved tumor penetration, and a combined chemo- and photothermal effect against 4T1 breast cancer. Importantly, Cur in CI-NPs reprogrammed the inflammatory microenvironment by reducing PTT-induced inflammatory cascades and downregulated the overexpressed HSP-70 to sensitize PTT. This enabled CI-NPs to significantly inhibit tumor growth and metastasis in vitro and in vivo. Therefore, this study provides a promising self-assembly strategy that combines phototherapeutic technique with natural small molecules, offering great potential for enhanced cancer therapy.