Near-infrared-triggered release of self-accelerating cascade nanoreactor delivered by macrophages for synergistic tumor photothermal therapy/starvation therapy/chemodynamic therapy

Macrophages have emerged as promising cellular vehicles for the delivery of therapeutic agents to tumor sites. However, the cytotoxicity of therapeutic agents toward the cellular carriers and the effective release of therapeutic agents at the tumor site remain the main challenges faced by macrophage-mediated drug delivery systems. Herein, a near-infrared (NIR)-triggered release of self-accelerating cascade nanoreactor (HCFG) delivered by macrophages (HCFG@R) was developed for synergistic tumor photothermal therapy (PTT)/starvation therapy (ST)/chemodynamic therapy (CDT). Attributed to the inherent tumor tropism of macrophages, HCFG@R could accumulate in tumor tissues and subsequently be disrupted by NIR laser, allowing the release of HCFG nanoparticles (NPs) from macrophage carriers. The released HCFG catalyzed the generation of O₂ from hydrogen peroxide (H₂O₂), which in turn enhanced glucose oxidase (GOx)-mediated ST. Simultaneously, the H₂O₂ and gluconic acid generated by ST could promote the production of hydroxyl radicals (·OH), thereby improving the therapeutic effect of CDT. The present study provides an innovative strategy for enhanced PTT/ST/CDT synergistic therapy through a macrophage-mediated delivery system.

Cascade nanoreactor; Macrophages; NIR-triggered release; Synergistic therapy; Targeted delivery.