Microenvironment-driven sequential ferroptosis, photodynamic therapy, and chemotherapy for targeted breast cancer therapy by a cancer-cell-membrane-coated nanoscale metal-organic framework

Designing and developing nanomedicine based on the tumor microenvironment (TME) for effective cancer treatment is highly desirable. In this work, polyvinyl pyrrolidone (PVP) dispersed nanoscale metal-organic framework (NMOF) of Fe-TCPP (TCPP = tetrakis (4-carboxyphenyl) porphyrin) loaded with hypoxia-activable prodrug tirapazamine (TPZ) and coated by the cancer cell membrane (CM) is constructed (the formed nano composite denoted as PFTT@CM). Due to the functionalization with the homologous cancer cell membrane, PFTT@CM is camouflaged to evade the immune clearance and preferentially accumulates at the tumor site. Once internalized by cancer cells, PFTT@CM is activated by the TME through redox reaction and Fenton reaction between Fe(3+ i)n nano-platform and endogenous glutathione (GSH) and hydrogen peroxide (H2O2) to promote GSH exhausting as well as .OH and O-2 production, which triggers ferroptosis and dramatically enhances photodynamic therapy (PDT) efficacy. Subsequently, the PDT process mediated by TCPP and light would consume oxygen and aggravate tumor hypoxia to further activate the prodrug TPZ for cancer chemotherapy. As a consequence, the TME-driven PFTT@CM nano-platform not only demonstrated its TME modulation ability but also showed a sequential synergistic therapy, which eventually inhibited the cancer cell proliferation. This multimodal nano-platform is expected to shed light on the design of TME-activatable reaction to reinforce the synergistic therapeutic outcome and facilitate the development of effective cancer nanomedicine.

Automated summary

In this study, a nanomedicine based on the tumor microenvironment (TME) was designed and developed for effective cancer treatment. The nanocomposite with a cancer cell membrane (CM) coating can evade the immune clearance and accumulate at the tumor site. Activation of the nanocomposite in the TME triggers a series of reactions, promoting cancer cell death and enhancing photodynamic therapy (PDT) efficacy. This sequential synergistic therapy has demonstrated the ability to inhibit cancer cell proliferation effectively.