NIR-light triggered photodynamic therapy combined with hypoxia activated chemotherapy for anti-tumor effects

Abstract

Photodynamic therapy (PDT) represents a promising non-invasive modality for clinical cancer treatment. However, its efficacy is constrained by the limited penetration depth of excitation light for most photosensitizers and therapy-induced hypoxia within the tumor microenvironment (TME). To overcome these limitations, we rationally designed a composite upconversion nanoparticle, UCNPs@MSN-Ce6/TPZ (UMCT), integrating the photosensitizer chlorin e6 (Ce6) and the hypoxia-activated prodrug tirapazamine (TPZ) for synergistic PDT and chemotherapy. Utilizing the unique properties of upconversion nanoparticles, UMCT generates singlet oxygen (¹O₂) via Ce6 activation upon 980 nm near-infrared (NIR) light irradiation, thereby initiating PDT. Concurrently, TPZ exploits both the PDT-aggravated hypoxia and the intrinsically hypoxic TME to exert its tumoricidal effects. Significantly, UMCT shows effective accumulation at the tumor site, achieving a potent and synergistic tumor-suppressing effect both in vitro and in vivo. This work provides a promising strategy for designing more efficient PDT nanoplatforms and advancing their biomedical applications.