Metal organic framework and doxorubicin co-encapsulated pH-responsive hydrogels against breast cancer through synergistic therapy

Abstract

Iron-based metal organic framework (Fe-MOF) is first synthesized by using tetra(4-carboxyphenyl)-porphyrin (TCPP) as the organic building blocks, which is then co-encapsulated with doxorubicin (DOX) in the oxidized sodium alginate (OSA)/carboxymethyl chitosan (CMCS) hydrogels cross-linked through the Schiff base reaction. The imine bonds (–HC=N–) between OSA and CMCS can be hydrolyzed in the acidic tumor microenvironment (TME), resulting in the release of DOX and Fe-MOF. The Fe-MOF can be further decomposed by the acidic TME to release TCPP and Fe3+. Oxygen molecules are catalyzed to singlet oxygen (1O2) by the photosensitizer TCPP upon exposure to near infrared (NIR) light, and the generated 1O2 can bring about photodynamic therapy (PDT). Additionally, the released Fe3+ can be reduced to Fe2+ by glutathione (GSH), which can react with H2O2 in the TME through the Fenton reaction to generate hydroxyl radicals (·OH) for chemodynamic therapy (CDT). Due to the synergistic therapy of PDT, CDT and chemotherapy, the Fe-MOF/DOX/OSA/CMCS hydrogels exhibit significant cytotoxicity against murine breast cancer cell line 4T1.