A cucurbit[7]uril-based upconversion nanoplatform for targeted photodynamic drug delivery

Photodynamic therapy (PDT) relies on light irradiation to induce the photochemical reaction of photosensitizers to convert oxygen (O₂) into highly cytotoxic reactive oxygen species (ROS). However, its therapeutic efficacy is limited by the intracellular oxygen concentration in tumor cells and the limited tissue penetration of the excitation light. Herein, we report a cucurbit[7]uril (CB[7])-mediated upconversion nanoplatform co-loaded with AS1411-C15/Hemin (AH) and the photosensitizer triphenylporphyrin derivative (TPP). Through electrostatic adsorption between upconversion nanoparticles (UCNPs) and CB[7], the co-delivery of AH and TPP is achieved via the host-guest interaction between CB[7] and adamantane (Ad). Specifically, AH can target and recognize nucleolin overexpressed on cancer cells, while acting as a horseradish peroxidase-mimicking catalyst to convert endogenous hydrogen peroxide into O₂, thereby overcoming the tumor's hypoxic microenvironment. In addition, the UCNPs convert the near-infrared laser, which offers deeper tissue penetration, into short-wavelength light. This further activates TPP to transform O₂ into singlet oxygen (¹O₂), effectively promoting cancer cell apoptosis. Experimental results demonstrate that this multifunctional upconversion nanoplatform provides an effective strategy for targeted photodynamic drug delivery.