Liposomes as drug vehicles have advantages, such as payload protection, tunable carrying capacity and improved biodistribution. However, due to the dysfunction of targeting moieties and payload loss during preparation, immunoliposomes have yet to be favoured in commercial manufacturing. Here we report a chemical modification-free biophysical approach for producing immunoliposomes in one step through the self-assembly of a chimeric nanobody (cNB) into liposome bilayers. cNB consists of a nanobody against human epidermal growth factor receptor 2 (HER2), a flexible peptide linker and a hydrophobic single transmembrane domain. We determined that 64% of therapeutic compounds can be encapsulated into 100-nm liposomes, and up to 2,500 cNBs can be anchored on liposomal membranes without steric hindrance under facile conditions. Subsequently, we demonstrate that drug-loaded immunoliposomes increase cytotoxicity on HER2-overexpressing cancer cell lines by 10- to 20-fold, inhibit the growth of xenograft tumours by 3.4-fold and improve survival by more than twofold.

脂质体作为药物载体具有有效负载保护、可调节的承载能力和改善的生物分布等优点。然而，由于靶向部分的功能障碍和制备过程中有效负载的损失，免疫脂质体尚未在商业生产中受到青睐。在这里，我们报告了一种无需化学修饰的生物物理方法，通过将嵌合纳米抗体（cNB）自组装成脂质体双层，一步生产免疫脂质体。 cNB 由针对人表皮生长因子受体 2 (HER2) 的纳米抗体、柔性肽接头和疏水性单跨膜结构域组成。我们确定 64% 的治疗化合物可以封装到 100 nm 脂质体中，并且在轻松的条件下可以将多达 2,500 个 cNB 锚定在脂质体膜上而没有空间位阻。随后，我们证明载药免疫脂质体可将 HER2 过表达癌细胞系的细胞毒性提高 10 至 20 倍，抑制异种移植肿瘤的生长 3.4 倍，并将生存率提高两倍以上。