Integrin-Targeted Delivery of Redox Homeostasis Regulating Lanthanide-Based Composite Nanoplatform for Deep Self-Enhanced Photodynamic/H₂S Gas Synergistic Therapy via 1530 nm Activation.

Abstract

As a non-invasive treatment for tumors, photodynamic therapy (PDT) still has several limitations. The high level of glutathione (GSH) in the tumor microenvironment (TME) and hypoxic characteristics significantly restrict the production of reactive oxygen species (ROS). Furthermore, the existing excitation light is unable to penetrate deep tissues, which extremely limits the effect of PDT on deep tumors. Herein, we develop a nanoplatform (UDNPs@MOF:DATS@cRGD-PEG, abbreviated as UMDP), which combines with upconversion/down-shifting nanoparticles (UDNPs), MOF composed of Fe³⁺ and meso-tetra(4-carboxyphenyl)porphine (TCPP), diallyl trisulfide (DATS), as well as active targeting peptide (cRGD-PEG). UDNPs can tune the excitation source to 1530 nm, which increases the penetration depth in vivo. MOF containing Fe³⁺ coated on UDNPs and DATS loaded in the MOF channel can regulate the levels of dissolved oxygen and GSH in the TME, improving ROS generation. H₂S generated by the reaction of DATS with GSH can produce a gas therapy (GT) effect. The active targeting effect of cRGD-PEG increases UMDP accumulation at the tumor site. The key advantage of UMDP lies in breakthrough tissue penetration depth and the mutually reinforcing therapy mechanisms, which overcome the bottleneck of traditional PDT and provide a novel strategy for enhancing the PDT/GT synergistic effect of deep-seated tumors.