Clinical Oncology Center, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
Institute of Oncology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, 200071, Shanghai, China.
J Mater Chem B. 2023 Apr 12;11(15):3453-3472. doi: 10.1039/d2tb02328h.
Combining chemotherapy and immunotherapy is a promising strategy for the treatment of non-small cell lung cancer (NSCLC) metastasis. However, platinum-based chemotherapeutics and immune checkpoint blockade-based cancer immunotherapy have toxic side effects and limitations. Ursolic acid (UA) and astragaloside IV (AS-IV) are natural compounds with anticancer activity sourced from Traditional Chinese medicine (TCM). However, their poor water solubilities and targeted deletions limit their medicinal value. In this study, we fabricated hyaluronic acid (HA)-modified UA/(AS-IV)-loaded polydopamine (PDA) nanomedicine (UA/(AS-IV)@PDA-HA) with a high yield at a low cost simple synthesis. This represents a novel multifunctional nanomedicine that combines chemotherapy, photothermal therapy (PTT), and immunotherapy with an active tumor-targeting ability. The as-prepared nanomedicine not only increased the aqueous solubilities of UA and AS-IV, but also improved their active targeting abilities. HA binds specifically to the overexpressed cluster of differentiation 44 (CD44) on the surface of most cancer cells, thereby improving drug targeting. While evaluating the anticancer effect of UA/(AS-IV)@PDA-HA and , the PDA nanodelivery system significantly improved UA-mediated cytotoxicity and anti-metastatic ability against NSCLC cells. In addition, the system also improved the AS-IV-mediated self-immune response of tumor-related antigens, which further inhibited the growth and distant metastasis of NSCLC. Further, PDA nanomaterial-mediated PTT inhibited tumor growth substantially. UA/(AS-IV)@PDA-HA not only significantly eradicated the primary tumor but also strongly inhibited the distant metastasis of NSCLC and . Thus, it has immense potential for development as an efficient anti-metastatic agent for NSCLC.
联合化疗和免疫治疗是治疗非小细胞肺癌（NSCLC）转移的一种有前途的策略。然而，铂类化疗药物和基于免疫检查点阻断的癌症免疫疗法具有毒副作用和局限性。熊果酸（UA）和黄芪甲苷 IV（AS-IV）是源自中药（TCM）的具有抗癌活性的天然化合物。然而，它们较差的水溶性和靶向缺失限制了它们的药用价值。在这项研究中，我们以低成本和简单的合成方法制备了透明质酸（HA）修饰的 UA/（AS-IV）负载聚多巴胺（PDA）纳米药物（UA/（AS-IV）@PDA-HA），产率高。这代表了一种新型多功能纳米药物，将化疗、光热治疗（PTT）和免疫治疗与主动肿瘤靶向能力相结合。所制备的纳米药物不仅增加了 UA 和 AS-IV 的水溶解度，而且提高了它们的主动靶向能力。HA 特异性结合到大多数癌细胞表面过表达的 CD44 上，从而提高了药物靶向性。在评估 UA/（AS-IV）@PDA-HA 的抗癌作用时，PDA 纳米递药系统显著提高了 UA 介导的对 NSCLC 细胞的细胞毒性和抗转移能力。此外，该系统还提高了 AS-IV 介导的肿瘤相关抗原的自身免疫反应，从而进一步抑制了 NSCLC 的生长和远处转移。此外，PDA 纳米材料介导的 PTT 显著抑制了肿瘤生长。UA/（AS-IV）@PDA-HA 不仅显著根除了原发肿瘤，而且强烈抑制了 NSCLC 的远处转移。因此，它作为 NSCLC 的有效抗转移剂具有巨大的发展潜力。
