A near-infrared light-responsive extracellular vesicle as a "Trojan horse" for tumor deep penetration and imaging-guided therapy.

Abstract How to make the nanoparticles evade immune surveillance and deeply penetrate the tumor tissues is of great importance to maximize the therapeutic efficacy of nanomedicines. Here, a near-infrared (NIR) light-responsive extracellular vesicle as a nanoplatform is developed to realize long circulation in blood, deep penetration in tumor tissues and rapid body elimination after the treatment. Like a “Trojan horse”, the nanoplatform is obtained by hiding the anti-tumor soldiers (DOX and 4.2 nm Ag2S quantum dots (QDs)) into the macrophage cell-secreted vesicle through electroporation. The natural composition and tumor targeting activity of the extracellular vesicles enable the nanoplatform to achieve a high accumulation in tumor and the in vivo biodistribution can be monitored by NIR fluorescence imaging of the Ag2S QDs. After the nanomedicines accumulate at the tumor sites, the soldiers will be released from the “Trojan horse” by utilizing the NIR photothermal effect of the Ag2S QDs. The released ultrasmall QDs and DOX can penetrate the whole tumor with a diameter of about 9 mm and effectively kill the tumor cells. Moreover, the inorganic QDs can be rapidly excreted from the body through renal clearance after the treatment to avoid the potential toxicity.