Chimeric nanobody-decorated liposomes by self-assembly

Md Mofizur Rahman, Jing Wang, Guosheng Wang, Zhipeng Su, Yizeng Li, Yundi Chen, Jinguo Meng, Yao Yao, Lefei Wang, Stephan Wilkens, Jifu Tan, Juntao Luo, Tao Zhang, Chuandong Zhu, Sung Hyun Cho, Lixue Wang, Luke P. Lee, Yuan Wan

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)818-824
Number of pages7
JournalNature Nanotechnology
Volume19
Issue number6
DOIs
StatePublished - Jun 2024

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2024.

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