pH-Responsive injectable self-healing hydrogels loading Au nanoparticles-decorated bimetallic organic frameworks for synergistic sonodynamic-chemodynamic-starvation-chemo therapy of cancer

A novel and efficient cancer therapy was developed using a smart hydrogel containing multifunctional bimetallic organic frameworks and anticancer drugs. The injectable self-healing hydrogel with pH-responsiveness was constructed through borate ester and imine bonds among dopamine-grafted sodium alginate (SADA), hydroxypropyl chitosan (HPCS) and 2-formylphenylboronic acid (2-FPBA). The Au nanoparticles-decorated Ti/Fe bimetallic organic framework tetragonal nanosheets (Au/TF-MOF TNS) were synthesized and incorporated into the hydrogel with the anticancer drugs doxorubicin (DOX). Upon intratumoral injection of nanocomposite hydrogel, the acidic tumor microenvironment triggered the cleavage of borate ester and imine bonds, causing the hydrogel to break down and accelerating the release of both Au/TF-MOF TNS and DOX. These Au/TF-MOF TNS functioned as nanozymes, producing hydroxyl radicals (·OH) for chemodynamic therapy (CDT), generating oxygen (O 2 ) to support sonodynamic therapy (SDT), and depleting glucose for starvation therapy (ST). Additionally, the Au/TF-MOF TNS served as sonosensitizers, capable of converting O 2 into singlet oxygen ( 1 O 2 ) upon ultrasound irradiation to achieve SDT. Therefore, this nanocomposite hydrogel system enabled synergistic sonodynamic-chemodynamic-starvation-chemo therapy (SDT-CDT-ST-CT) of cancer, presenting a promising platform for advanced cancer therapy strategies.