Self-healable oxide sodium alginate/carboxymethyl chitosan nanocomposite hydrogel loading Cu2+-doped MOF for enhanced synergistic and precise cancer therapy

The limitations of traditional therapeutic methods such as chemotherapy serious restricted the application in tumor treatment, including poor targeting, toxic side effects and poor precision. It is important to develop non-chemotherapeutic systems to achieve precise and efficient tumor treatment. Therefore, a functional metal-organic framework material (MOF) with porphyrin core and doped with Cu2+ and surface-modified with polydopamine (PDA), namely PCN-224(Cu)@PDA (PCP) was designed and prepared. After loaded into the injectable and self-healable hydrogels by dynamic Schiff base bonding of oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMC), the multifunctional nanocomposite hydrogels were obtained, in which Cu2+ in MOF converts to Cu+ by reacting with glutathione (GSH) which reduces the tumor antioxidant activity to improve the CDT effect. The Cu2+/Cu+ induces Fenton-like reaction in tumor cells to produce a toxic hydroxyl radical (OH). PDA achieves photothermal conversion under NIR light for photothermal therapy (PTT), and porphyrin core as a ligand generates reactive oxygen species (ROS), presenting highly efficient photodynamic therapy (PDT). Injectable self-healing hydrogel as a loading platform can be in situ injected to tumor site to release PCP and endocytosed by tumor cells to achieve precise and synergistic CDT-PDT-PTT therapy.