A ZIF-82-based nanoreactor for tumor-specific nitric oxide release and enhanced photodynamic therapy under NIR-II imaging guidance.

Abstract

Cancer remains a critical global health challenge, with conventional treatments often limited by systemic toxicity, therapeutic resistance, and inadequate penetration into deep tumor tissues. To address these issues, we developed UC-ZIF/MC540-an integrated nanoplatform combining Ce³⁺-doped upconversion nanoparticles (UCNPs) with the photosensitizer Merocyanine 540 within a ZIF-82 metal-organic framework. Under 980 nm near-infrared irradiation, the UCNPs emit visible light at 540 nm, activating MC540 to generate reactive oxygen species for photodynamic therapy (PDT). Simultaneously, the ZIF-82 component responds to tumor microenvironmental cues, including acidity, hypoxia, and radiation, to release nitric oxide (NO), which suppresses HSP70 expression and synergistically enhances PDT efficacy. Furthermore, the Ce³⁺ doping enhances emission in the NIR-IIb window (1525 nm), facilitating high-resolution deep-tissue imaging and precise tracking of nanoparticle distribution. This multifunctional system enables a combined therapeutic and diagnostic strategy for effective treatment of melanoma and other deep-seated tumors.