A hierarchical supramolecular nanozyme platform for programming tumor-specific PDT and catalytic therapy

Supramolecular chemistry as a promising tool bridges the gap between conveniently synthetic processes and multifunction through reversible noncovalent interactions. Herein, a supramolecular nanoplatform, AuP-PS , is built by flexible and reversible supramolecular interactions between pillar[5]arene-capped gold nanoparticles ( AuP s) and porphyrin-containing “V” shape block copolymers ( PS ). The biosafety of AuP-PS was greatly improved by the formation of supramolecular complexes. Taking advantage of gradient pH changes in the tumor microenvironment (TME), AuP-PS can first disassemble into single AuP-PS nanoparticles due to the pH-sensitive DPA units of PS under pH = 6.5 and enter into the in-depth tumor sites. Whereafter, single AuP-PS nanoparticles completely dissociate, release PS and expose AuP s due to the reversible host-guest interaction at pH = 5.4, where photodynamic therapy and catalytic therapy were sufficiently activated to combat against the in-depth tumor. In vitro results indicate that the singlet oxygen yield of supramolecular AuP-PS nanoplatform was amplified 5.6 times under pH = 5.4 than that under pH = 7.4, and the nanozyme activity of AuP-PS nanoplatform was dramatically boosted 6.7 times than that of the control sample without reversible linkers under pH = 5.4. In vivo data further reveal that the supramolecular AuP-PS nanoplatform displayed superb therapeutic efficacy. Hence, this supramolecular AuP-PS nanoplatform may provide a programmed and complementary synergistic therapy strategy for in-depth and efficient treatment for solid tumors.