Arsenic trioxide (ATO, As₂O₃), an active ingredient of traditional Chinese medicine, has been approved by the U.S. Food and Drug Administration as an effective therapeutic agent for acute promyelocytic leukemia (APL). However, the application of ATO in treating advanced solid tumors like hepatocellular carcinoma (HCC) is still restricted by limited therapeutic efficacy and insufferable side effects. To solve this problem, we reported a general and facile strategy using human serum albumin (HSA) as a template for synthesizing a series of ATO-based nanoparticles with uniform single-albumin size. Then, we prepared a multifunctional drug delivery system (MDDS) based on MnAs/HSA termed MnAs/ICG/HSA-RGD, and tested its efficacy both in vitro and in vivo. Our results revealed that the photothermal effect of MnAs/ICG/HSA-RGD can not only cause irreversible damage to the tumor but also accelerate the discharge of As and Mn²⁺ ions, enabling responsive chemotherapy and magnetic resonance imaging. Interestingly, the expression of HSP90, vimentin, and MMP-9 in tumor cells was inhibited during the treatment, resulting in less metastasis and recurrence. Moreover, no apparent side effect has been observed during the treatment. Therefore, MnAs/ICG/HSA-RGD can be considered as a promising option for HCC with excellent therapeutic efficacy and minimum side effects.

中文翻译：

---

载亚砷酸盐的白蛋白纳米颗粒用于 HCC 的靶向协同化学光热治疗

三氧化二砷（ATO，As ₂ O ₃）是一种中药活性成分，已被美国食品和药物管理局批准为急性早幼粒细胞白血病（APL）的有效治疗剂。然而，ATO在治疗肝细胞癌（HCC）等晚期实体瘤中的应用仍受到疗效有限和副作用难以忍受的限制。为了解决这个问题，我们报告了一种使用人血清白蛋白 (HSA) 作为模板合成一系列具有均匀单白蛋白大小的基于 ATO 的纳米粒子的通用且简便的策略。然后，我们制备了一种基于 MnAs/HSA 的多功能给药系统 (MDDS)，称为 MnAs/ICG/HSA-RGD，并在体外和体内。我们的研究结果表明，MnAs/ICG/HSA-RGD 的光热效应不仅可以对肿瘤造成不可逆的损伤，还可以加速 As 和 Mn ²⁺离子的释放，从而实现响应性化疗和磁共振成像。有趣的是，治疗过程中肿瘤细胞中HSP90、波形蛋白和MMP-9的表达受到抑制，从而减少了转移和复发。此外，在治疗过程中没有观察到明显的副作用。因此，MnAs/ICG/HSA-RGD 可以被认为是 HCC 的一种有前途的选择，具有出色的治疗效果和最小的副作用。