Photothermal-magnetic driven post-targeting retention and cascade therapy of “biomimetic glue”-based nanoreactor for cancer theranostics by bystander-like killing

Abstract

The high interstitial fluid pressure (IFP) in tumors can force nanoparticles back into circulation, resulting in shorter intra-tumor retention that significantly affects their diagnostic and therapeutic abilities. The self-assembly of nanoparticles within tumor tissues can markedly enhance their in situ retention. We fabricated a sea urchin-shaped nanoreactor with an average size of 85.6 nm by coating nano carbonyl iron powder (nano-CIP) with Fe₃O₄, and modified the surface with platelet membrane (PM). The CIP@Fe₃O₄@PM nanoreactor exhibited photothermal-magnetic property with photothermal conversion efficiency of 46.1 % and saturation magnetization reached 204.8 emu/g. The CIP@Fe₃O₄@PM nanoreactor self-assembled at the tumor site due to magnetic aggregation and photothermal-induced platelet recruitment. The enhanced tumor retention of CIP@Fe₃O₄@PM upon magnetic stimulation and NIR irradiation generated a light-heat-gas cascade reaction, which enabled multi-modal (MRI/CT/FTI/US) tumor imaging and synergistic photothermal/gas/ferroptosis therapy in a mouse model of melanoma, achieving a remarkable tumor growth inhibition of 82.39 %. In addition, the increased CIP@Fe₃O₄@PM nanoreactor accumulation in the extracellular matrix resulted in a “bystander-like killing” effect on the tumor, and achieved imaging-guided tumor ablation. Taken together, this “biomimetic glue”-based CIP@Fe₃O₄@PM nanoreactor is a promising option for melanoma theranostics, and illustrates a novel strategy for photothermally and magnetically driven post-targeting retention of nanoparticles.