Reversing insufficient photothermal therapy-induced tumor relapse and metastasis by regulating cancer-associated fibroblasts

Insufficient tumor accumulation and distribution of photosensitizers as well as low antitumor immunity severely restrict the therapeutic efficacy of photothermal therapy (PTT). Cancer-associated fibroblasts (CAFs) play a key role in tumor extracellular matrix (ECM) remodeling and immune evasion. Reshaping tumor microenvironment via CAF regulation might provide a potential approach for complete tumor elimination in combination with PTT. Here, tumor cell-derived microparticles co-delivering calcipotriol and Indocyanine green (Cal/ICG@MPs) are developed to modulate CAFs for improved PTT efficacy. Cal/ICG@MPs efficiently target tumor tissues and regulate CAFs to reduce tumor ECM, resulting in enhanced tumor accumulation and penetration of ICG to generate strong PTT efficacy and activate CD8(+) T cell-mediated antitumor immunity. In addition, Cal/ICG@MPs-triggered CAF regulation enhances tumor infiltration of CD8(+) T cells and ameliorates CAF-induced antigen-mediated activation-induced cell death of tumor-specific CD8(+) T cells in response to PTT, eliciting long-term antitumor immune memory to inhibit tumor recurrence and metastasis. Our results support Cal/ICG@MPs as a promising drug to improve PTT efficacy in cancer treatment. Photothermal therapy (PTT) has emerged as a promising approach for cancer treatment. Here, in preclinical cancer models, the authors show that PTT efficacy could be improved using tumor cell-derived microparticles that co-deliver the photosensitizer indocyanine green and a vitamin-D receptor ligand, calcipotriol, resulting in tumor extracellular matrix remodelling and ameliorated anti-tumor immune responses.

Automated summary

The study demonstrates that co-delivery of indocyanine green and calcipotriol using tumor cell-derived microparticles can enhance the efficacy of photothermal therapy by remodeling the tumor extracellular matrix and improving anti-tumor immune responses.