Perihilar cholangiocarcinoma (PHCC) presents a formidable challenge due to its occult anatomic location, aggressive growth, insensitivity to conventional chemotherapy, and poor prognosis. Herein, we engineered a human epidermal growth factor receptor 2 (HER2) affibody to the surface of cell membrane nanovesicles (A-NVs) in a ligand-oriented manner and loaded them with indocyanine green (ICG) as precision theranostics for PHCC treatment. The A-NVs@ICG were prepared and exhibited satisfactory targeting effects in HER2-overexpressing PHCC cells. In vivo fluorescence and photoacoustic imaging demonstrated that A-NVs@ICG promoted the accumulation of ICG in PHCC tissue, leading to enhanced tumor regression and improved anti-cancer effects when combined with photoirradiation. Therefore, bio-engineered A-NVs@ICG represent a promising nanotheranostic agent for PHCC with potential for clinical translation.

中文翻译：

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生物工程细胞膜纳米囊泡作为肝周胆管癌的精确治疗方法

肝门周围胆管癌（PHCC）由于其隐匿的解剖位置，侵袭性生长，对常规化学疗法不敏感以及预后不良而面临着巨大的挑战。在本文中，我们以面向配体的方式将人表皮生长因子受体2（HER2）亲和体工程化到细胞膜纳米囊泡（A-NVs）的表面，并用吲哚菁绿（ICG）装载它们作为用于PHCC治疗的精确治疗方法。制备了A-NVs @ ICG，并在过表达HER2的PHCC细胞中表现出令人满意的靶向作用。体内荧光和光声成像表明，A-NVs @ ICG促进了PHCC组织中ICG的积累，与光辐照结合使用可增强肿瘤消退并改善抗癌效果。因此，生物工程化的A-NVs @ ICG代表了有前途的PHCC纳米治疗剂，具有临床翻译潜力。