NIR-Programmed Trimodal Macrophage Nanovectors for Effective Anti-Tumor Therapy in Mice Model

Introduction: Chemotherapy remains the primary treatment modality for advanced and unresectable tumors; however, its antitumor efficacy is limited, and it has significant toxic effects on normal tissues.

Methods: To address these challenges, cell carrier- and nanomaterial-based strategies were employed in this study to engineer macrophages into functional "Trojan horses" loaded with ICG-CDDP mesoporous silicon nanoparticles, yielding an intelligent cell carrier chemotherapeutic drug delivery system with controlled light responsiveness and "on-demand" nanophotothermolysis capabilities.

Results: Our findings demonstrate that the intelligent macrophage drug delivery system actively homes to tumor sites and that indocyanine green (ICG) fluorescence can be used to visualize exogenous macrophages at the tumor site. In response irradiation of the delivery area with exogenous near-infrared (NIR) light, ICG generates a thermal effect, resulting in the lysis of macrophages and facilitating spatiotemporally controlled burst release of intracellular cisplatin, thereby precisely targeting tumor cells. Simultaneously, ICG can trigger immunogenic cell death (ICD) under NIR irradiation, transforming "cold tumors" into "hot tumors" and eliciting a prolonged antitumor immune response, thereby overcoming the limitations associated with chemotherapeutic drugs.

Conclusion: This collaborative trimodal strategy successfully represents a triple breakthrough in precise delivery, spatiotemporally controlled drug release, and immune activation. It is an innovative solution for the precise treatment of advanced tumors and has substantial potential for clinical translation.

ICD; immunogenic cell death; macrophage-mediated drug delivery; spatiotemporally controlled release; trimodal therapy.