Tumor metastasis is a major cause of poor cancer prognosis. Photothermal therapy (PTT) is a non-invasive, non-oxygen-dependent, and highly spatiotemporally precise treatment that may aid chemotherapy in suppressing tumor growth and metastasis. This article aims to develop and modify a CuS-based nanoplatform linking RGD-Acrk to actively target and internalize doxorubicin (DOX) into tumor cells, resulting in an alternating strategy of synergistic chemo/PTT. The nanoparticle’s shape, spectra, drug encapsulation efficiency, loading content, and controlled release are characterized, and a comparison of 808/980 nm lasers is used to irradiate the nanoplatform. The cell survival rate is used to determine the cytotoxicity of DOX and PTT, and the chemo/PTT is used to treat 4T1-Luc tumor-bearing mice. Simultaneously, bioluminescence and photoacoustic imaging are employed to assess therapy efficacy, as well as tumor size, weight, density, the bodyweight of mice, and survival curves. H&E, immunohistochemistry for HIF-1, and TUNEL fluorescence staining confirm these findings, suggesting that the nanoplatform has a good active-targeted capacity and perform high-efficiency PTT caused by 980 nm laser irradiation. The synergistic effect is at least 3.53 times higher than chemo/PTT without synergistic effect and tumor liver metastasis is successfully suppressed, showing that it has the potential to be used for cancer treatment and prognosis improvement.

肿瘤转移是癌症预后不良的主要原因。光热疗法 (PTT) 是一种非侵入性、非氧依赖性和高度时空精确的治疗方法，可帮助化学疗法抑制肿瘤生长和转移。本文旨在开发和修改连接 RGD-Acrk 的基于 CuS 的纳米平台，以主动靶向和内化阿霉素 (DOX) 进入肿瘤细胞，从而形成协同化疗/PTT 的交替策略。表征了纳米颗粒的形状、光谱、药物包封效率、负载量和控释，并比较了 808/980 nm 激光照射纳米平台。细胞存活率用于确定 DOX 和 PTT 的细胞毒性，化疗/PTT 用于治疗 4T1-Luc 荷瘤小鼠。同时，生物发光和光声成像用于评估治疗效果，以及肿瘤大小、重量、密度、小鼠体重和生存曲线。H&E、HIF-1 的免疫组织化学和 TUNEL 荧光染色证实了这些发现，表明该纳米平台具有良好的主动靶向能力，并且可以执行由 980 nm 激光照射引起的高效 PTT。协同作用比无协同作用的化疗/PTT至少高3.53倍，成功抑制肿瘤肝转移，表明其具有用于癌症治疗和改善预后的潜力。和 TUNEL 荧光染色证实了这些发现，表明该纳米平台具有良好的活性靶向能力，并执行由 980 nm 激光照射引起的高效 PTT。协同作用比无协同作用的化疗/PTT至少高3.53倍，成功抑制肿瘤肝转移，表明其具有用于癌症治疗和改善预后的潜力。和 TUNEL 荧光染色证实了这些发现，表明该纳米平台具有良好的活性靶向能力，并执行由 980 nm 激光照射引起的高效 PTT。协同作用比无协同作用的化疗/PTT至少高3.53倍，成功抑制肿瘤肝转移，表明其具有用于癌症治疗和改善预后的潜力。