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.
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Data availability
The authors declare that all data supporting the findings of this study are available within the paper and Supplementary Information files. Additional information and unique biological materials can be requested from the corresponding author upon reasonable request. Custom code was not involved in this study.
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Acknowledgements
Y.W. thanks the support from National Cancer Institute R01CA230339 and R37CA255948. Y.L. is supported by NSF 2303648. The opinions, findings, conclusions or recommendations expressed are those of the authors and do not necessarily reflect the views of any of the funding agencies. L.W. thanks the support from Jiangsu Provincial Medical Youth Talent QNRC2016054 and the Leading-Edge Technology Program of Jiangsu Natural Science Foundation BK20212012. S.H.C. thanks the support from office of the Direct, National Institutes of Health S10OD026822-01.
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The project was designed by Y.W., Lixue W. and L.P.L. M.R., J.W., G.W., Z.S., Y.L., Y.C., J.M., Y.Y., Lefei W., S.W., J.T., J.L., T.Z., C.Z. and S.H.C. performed the experiments, collected and analysed the data. All authors contributed to the writing of the paper, discussed the results and implications, and edited the paper at all stages.
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Rahman, M.M., Wang, J., Wang, G. et al. Chimeric nanobody-decorated liposomes by self-assembly. Nat. Nanotechnol. (2024). https://doi.org/10.1038/s41565-024-01620-6
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DOI: https://doi.org/10.1038/s41565-024-01620-6