In Situ Transformable Nanoplatforms with Supramolecular Cross‐Linking Triggered Complementary Function for Enhanced Cancer Photodynamic Therapy

Abstract

In vivo cross-linking of nanoparticles is widely used to increase accumulation of therapeutic agents at tumor site for enhanced therapy. However, the components in nanoplatforms usually only play for one role and are independent of each other, unable to amplify their biofunctions. Herein, a complementary functioning tumor microenvironment triggered, supramolecular coordination-induced nanoparticle cross-linking strategy is constructed for enhanced photodynamic therapy. Manganese oxide (MnO_x ) and polyhydroxy photosensitizer hypericin (Hyp) are coated and loaded onto lanthanide-doped upconversion nanoparticles (UCNPs) to form transformable UCNP@MnO_x -Hyp. In CT26 mouse colon cancer cells and xenograft tumors, UCNP@MnO_x -Hyp is reduced by glutathione and H₂ O₂ , releasing Mn²⁺ and Hyp for in situ cross-linking to transform to UCNP@Mn²⁺ -Hyp. Compared to the simple photosensitizer-loaded UCNP@PEI-Hyp, the Mn²⁺ -Hyp coordination redshifts absorbance of Hyp and improves the energy transfer efficiency from UCNPs to Hyp (5.6-fold). In turn, the supramolecular coordination-induced UCNPs cross-linking exhibits enhanced luminescence recovery and increased intracellular accumulation of both UCNPs and Hyp, thus enhancing the photodynamic therapy efficacy both at cellular level (2.1-fold) and in vivo, realizing the function amplification of each component after responsive transformation and offering a new avenue for enhanced cancer therapy.