Design and synthesis of cancer-cell-membrane-camouflaged hemoporfin-Cu 9 S 8 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-Cu ₉ S ₈ 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 Cu ₉ S ₈ as photothermal agents and carriers have been obtained through sulfurizing cuprous oxide (Cu ₂ O) nanoparticles through "Kirkendall effect", and they exhibit hollow nanospheres structure with a size of ∼200 nm. Then, Cu ₉ S ₈ nanospheres could be used to load with hemoporfin sonosensitizers, and then hemoporfin-Cu ₉ S ₈ nanospheres (abbreviated as H-Cu ₉ S ₈ ) can be further surface-camouflaged with CCM. H-Cu ₉ S ₈ @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 ¹ O ₂ for subsequent SDT. Especially, H-Cu ₉ S ₈ @CCM NPs are featured with biocompatibility and homologous targeting capacity. When intravenously (i.v.) injected into mice, H-Cu ₉ S ₈ @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-Cu ₉ S ₈ NPs (0.49 h, 9.68% ID/g) without CCM. In addition, upon 1064 nm laser and ultrasound irradiation, H-Cu ₉ S ₈ @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.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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