Design and synthesis of cancer-cell-membrane-camouflaged hemoporfin-Cu9S8 nanoagents for homotypic tumor-targeted photothermal-sonodynamic therapy

Multimodal therapies have aroused great interest in tumor therapy due to their highly effective antitumor effect. However, immune clearance limits the practical application of nanoagents-based multimodal therapies. To solve this problem, we have designed hemoporfin-Cu9S8 hollow nanospheres camouflaged with the CT26 cell membrane (CCM) as a model of multifunctional agents, achieving homologous-targeted synergistic photothermal therapy (PTT) and sonodynamic therapy (SDT). Hollow Cu9S8 as photothermal agents and carriers have been obtained through sulfurizing cuprous oxide (Cu2O) nanoparticles through “Kirkendall effect”, and they exhibit hollow nanospheres structure with a size of ∼200 nm. Then, Cu9S8 nanospheres could be used to load with hemoporfin sonosensitizers, and then hemoporfin-Cu9S8 nanospheres (abbreviated as H-Cu9S8) can be further surface-camouflaged with CCM. H-Cu9S8@CCM nanospheres exhibit a broad photoabsorption in the range of 700–1100 nm and high photothermal conversion efficiency of 39.8% under 1064 nm laser irradiation for subsequent PTT. In addition, under the excitation of ultrasound, the loaded hemoporfin could generate 1O2 for subsequent SDT. Especially, H-Cu9S8@CCM NPs are featured with biocompatibility and homologous targeting capacity. When intravenously (i.v.) injected into mice, H-Cu9S8@CCM NPs display a higher blood circulation half-life (3.17 h, 6.47 times) and tumor accumulation amount (18.75% ID/g, 1.94 times), compared to H-Cu9S8 NPs (0.49 h, 9.68% ID/g) without CCM. In addition, upon 1064 nm laser and ultrasound irradiation, H-Cu9S8@CCM NPs can inhibit tumor growth more efficiently due to high accumulation efficiency and synergistic PTT-SDT functions. Therefore, the present study provides some insight into the design of multifunctional efficient agents for homotypic tumor-targeted therapy.