Engineered biomimetic nanoreactor for synergistic photodynamic-chemotherapy against hypoxic tumor

Photodynamic therapy (PDT) can produce a large amount of reactive oxygen species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microen-vironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemo-therapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT). Then, PIT was camouflaged with cyclic arginine-glycine-aspartate (cRGD) modified tumor cell membranes to obtain the engineered membrane-coated nanoreactor (cRGD-mPIT). The nanoreactor cRGD-mPIT could achieve the dual-targeting ability via tumor cell membrane mediated homologous targeting and cRGD mediated active targeting. With the enhanced tumor-targeting and penetrating delivery system, PIT could efficiently accumulate in hypoxic tumor cells and the loaded drugs were quickly released in response to near-infrared (NIR) laser. The nanoreactor might produce cytotoxic ROS under NIR and further enhance hypoxia within tumor to activate TPZ, which efficiently inhibited hypoxic tumor by synergistic photodynamic-chemotherapy. Mechanically, hypoxia-inhibitory factor-1 alpha (HIF-1 alpha) was down-regulated by the synergistic therapy. Accordingly, the cRGD-mPIT nanoreactor with sustainable and cascade anti-tumor effects and satisfied biosafety might be a promising strategy in hypoxic tumor therapy.

Automated summary

In this study, a nanoreactor was constructed by loading indocyanine green and tirapazamine on mesoporous polydopamine and camouflaging it with tumor cell membrane. The nanoreactor exhibited dual-targeting ability and sustained treatment for hypoxic tumors. With the activation of near-infrared laser, the nanoreactor produced cytotoxic reactive oxygen species and inhibited tumor growth by down-regulating hypoxia-inhibitory factor-1 alpha.