Light-activated nitric-oxide overproduction theranostic nanoplatform based on long-circulating biomimetic nanoerythrocyte for enhanced cancer gas therapy

The limited intratumoral perfusion of nitric oxide(NO)-carrying nanoparticles into solid tumors caused by the inherent biological barriers in vivo greatly attenuates their generated efficacy. Herein, through entrapping heat-sensitive NO donors(BNN6)on mesoporous polydopamine nanoparticles(M-PDA) and subsequently enveloping with red blood cells membranes, a heatresponsive biomimetic theranostic nanoerythrocyte(M/B@R) is developed to boost NO-based cancer therapy. The reserved intact structure of red blood cells membranes(RBCm) endows M/B@R with superior biosafety and stealth properties for prolonged circulation time and subsequent enhanced tumor accumulation. Once internalized in tumors and excited by nearinfrared light(NIR, 808 nm) irradiation, M/B@R can not only yield plenty of heat for photothermal therapy(PTT) but also achieve the overproduction of NO for highly-efficient NO gas therapy due to its high loading capacity and NIR-absorbing property of M-PDA. The generated NO further ensures the formation of ONOO^(-) which possesses remarkable toxicity to tumor as well as alleviating tumor hypoxia. It is found that M/B@R with NIR as the excitation source can significantly induce synthetic lethality to tumors via the hyperthermia, DNA damage and the ease of tumor hypoxia. Simultaneously, M/B@R also exhibits the potential for bimodal fluorescence and photothermal imaging. The RBCm-camouflaged NO delivery nanoplatform with bimodal imaging capability in this work may provide a new combinatorial paradigm to induce PTT/NO for cancer theranostic applications.