Nanoparticle flexibility is an important parameter in determining cell uptake and tumor accumulation, thus modulating therapeutic efficiency in cancer treatment. Herein, we successfully prepared CuS-embedded human serum albumin hollow nanocapsules (denoted CuS/HSA) by a hard-core-assisted layer-by-layer coating approach. This approach afforded CuS/HSA hollow nanocapsules with controllable shell thickness, tunable flexibility, uniform size (272.9 nm), a large hollow cavity, peroxidase-like activity, excellent photothermal conversion ability, and a high tetra-(4-aminophenyl) porphyrin (TAPP) loading capacity (27.3 wt%). The peroxidase-like activity of the CuS nanoparticles enabled them to overcome tumor hypoxia and augment the sonodynamic therapeutic (SDT) effects and photothermal conversion ability for photothermal therapy (PTT). In vitro experiments showed that the CuS/HSA-TAPP hollow nanocapsules efficiently induced cancer cell apoptosis under US irradiation and cancer cell ablation under laser irradiation, thus facilitating synergistic SDT and PTT. Importantly, the flexibility of the CuS/HSA hollow nanocapsules resulted in significantly enhanced cellular internalization and a longer mean residence time (131.3 h) than their solid counterparts (21.0 h). In a breast tumor model, the flexible CuS/HSA hollow nanocapsules exhibited high tumor accumulation of up to 27.1%. In vivo experiments demonstrated that the flexible CuS/HSA-TAPP hollow nanocapsules effectively eliminated breast tumors via the synergistic effect of SDT and PTT.

中文翻译：

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具有过氧化物酶样活性的柔性 CuS 包埋人血清白蛋白中空纳米胶囊用于协同声动力和光热癌症治疗

纳米颗粒的柔韧性是决定细胞摄取和肿瘤积累的重要参数，从而调节癌症治疗中的治疗效率。在此，我们通过硬核辅助的逐层包覆方法成功制备了 CuS 包埋的人血清白蛋白中空纳米胶囊（表示为 CuS/HSA）。这种方法提供的CuS/HSA中空纳米胶囊具有可控的壳厚度、可调的柔韧性、均匀的尺寸（272.9 nm）、大的中空腔、类过氧化物酶活性、优异的光热转换能力和高四（4-氨基苯基）卟啉。 TAPP) 负载能力 (27.3 wt%)。CuS纳米颗粒的过氧化物酶样活性使它们能够克服肿瘤缺氧并增强声动力治疗（SDT）效果和光热治疗（PTT）的光热转换能力。体外实验表明，CuS/HSA-TAPP 中空纳米胶囊在超声照射下有效诱导癌细胞凋亡，在激光照射下有效消融癌细胞，从而促进 SDT 和 PTT 的协同作用。重要的是，CuS/HSA 中空纳米胶囊的灵活性导致细胞内化显着增强，平均停留时间（131.3 小时）比固体对应物（21.0 小时）更长。在乳腺肿瘤模型中，柔性 CuS/HSA 中空纳米胶囊表现出高达 27.1% 的高肿瘤积累。体内实验表明，柔性 CuS/HSA-TAPP 中空纳米胶囊通过SDT 和 PTT 的协同作用有效地消除了乳腺肿瘤。