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

doi:10.1038/s41565-024-01620-6

Chimeric nanobody-decorated liposomes by self-assembly

Nat Nanotechnol. 2024 Feb 19. doi: 10.1038/s41565-024-01620-6. Online ahead of print.

Authors

Md Mofizur Rahman^#^{1

2}, Jing Wang^#^{3

4}, Guosheng Wang^#^{1

5}, Zhipeng Su⁶, Yizeng Li⁷, Yundi Chen¹, Jinguo Meng⁶, Yao Yao⁶, Lefei Wang⁶, Stephan Wilkens⁸, Jifu Tan⁹, Juntao Luo¹⁰, Tao Zhang¹¹, Chuandong Zhu^{1

12}, Sung Hyun Cho¹³, Lixue Wang^{14

15}, Luke P Lee^{16

17

18

19}, Yuan Wan²⁰

Affiliations

¹ The Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton University, Binghamton, NY, USA.
² Department of Pharmacy, Daffodil International University, Dhaka, Bangladesh.
³ Department of Hematology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
⁴ Department of Oncology and Hematology, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, China.
⁵ Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁶ Nanjing Regenecore Biotech Co. Ltd., Nanjing, China.
⁷ Biophysics and Mathematical Biology Lab, Department of Biomedical Engineering, Binghamton University, Binghamton, NY, USA.
⁸ Department of Biochemistry and Molecular Biology, Upstate Medical University, Syracuse, NY, USA.
⁹ Department of Mechanical Engineering, Northern Illinois University, Dekalb, IL, USA.
¹⁰ Department of Pharmacology, Upstate Medical University, Syracuse, NY, USA.
¹¹ School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, USA.
¹² Department of Radiotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.
¹³ Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA.
¹⁴ The Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton University, Binghamton, NY, USA. lixue.wang@njucm.edu.cn.
¹⁵ Department of Radiotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China. lixue.wang@njucm.edu.cn.
¹⁶ Harvard Medical School, Harvard University; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. lplee@bwh.harvard.edu.
¹⁷ Department of Bioengineering, Department of Electrical Engineering and Computer Science, University of California, Berkeley, CA, USA. lplee@bwh.harvard.edu.
¹⁸ Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, Korea. lplee@bwh.harvard.edu.
¹⁹ Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, Korea. lplee@bwh.harvard.edu.
²⁰ The Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton University, Binghamton, NY, USA. ywan@binghamton.edu.

^# Contributed equally.

PMID: 38374413
DOI: 10.1038/s41565-024-01620-6

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.