Near-Infrared-Responsive Metal–Organic Framework@NaLnF₄ Upconversion Nanoparticle Heterostructures for Advanced Photodynamic Theranostics

The short absorption wavelengths of conventional metal-organic frameworks (MOFs) severely limits their photodynamic therapy (PDT) applications due to poor tissue penetration. Integrating MOFs with upconversion nanoparticles (UCNPs) to harness their complementary advantages has emerged as a transformative strategy. Here, a near-infrared (NIR)-responsive core@shell heterostructure (UGD) was engineered integrating lanthanide-doped UCNPs (NaYF₄:20%Yb,2%Er@NaYF₄:20%Yb@NaNdF₄) with a boron-dipyrromethene (BODIPY)-based gadolinium metal-organic framework (GD). The UCNP core converts 808 nm NIR light into green emissions (515-564 nm) through cascade energy transfer (Nd³⁺ → Yb³⁺ → Er³⁺), precisely activating GD photosensitizers to enable effective ROS generation in deep tissues. In vitro studies revealed comparable cytotoxicity under 505 and 808 nm irradiation, while in vivo experiments demonstrated superior tumor suppression with 808 nm light (90% volume reduction vs 65% for 505 nm). Systematic biodistribution analysis confirmed tumor-targeted accumulation and rapid metabolic clearance. The UGD platform synergizes NIR penetration depth with MOF-enhanced photosensitizer stability, offering a transformative strategy for precision photodynamic theranostics.