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Harvard Medical School / UC Berkeley

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Nat. Nanotechnol., Feb 19 2024, | https://doi.org/10.1038/s41565-024-01620-6 Chimeric nanobody-decorated liposomes by self-assembly

Md. Mofizur Rahman^1,2,18, Jing Wang ^3,4,18, Guosheng Wang^1,5,18, Zhipeng Su ⁶, Yizeng Li ⁷, Yundi Chen ¹, Jinguo Meng ⁶, Yao Yao ⁶, Lefei Wang⁶, Stephan Wilkens ⁸, Jifu Tan ⁹, Juntao Luo ¹⁰, Tao Zhang ¹¹, Chuandong Zhu ^1,12, Sung Hyun Cho ¹³, Lixue Wang ^1,12, Luke P. Lee ^14,15,16,17& Yuan Wan ¹

¹The Pq Laboratory of BiomeDx/Rx, Department of Biomedical Engineering, Binghamton University, Binghamton, NY, USA.

²Department of Pharmacy, Daffodil International University, Dhaka, Bangladesh.

³Department of Hematology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.

⁴Department of Oncology and Hematology, Yizheng Hospital of Nanjing Drum Tower Hospital Group, Yizheng, China.

⁵Department of Pulmonary and Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

⁶Nanjing Regenecore Biotech Co. Ltd., Nanjing, China.

⁷Biophysics and Mathematical Biology Lab, Department of Biomedical Engineering, Binghamton University, Binghamton, NY, USA.

⁸Department of Biochemistry and Molecular Biology, Upstate Medical University, Syracuse, NY, USA.

⁹Department of Mechanical Engineering, Northern Illinois University, Dekalb, IL, USA.

¹⁰Department of Pharmacology, Upstate Medical University, Syracuse, NY, USA.

¹¹School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, NY, USA.

¹²Department of Radiotherapy, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China.

¹³Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, USA.

¹⁴Harvard Medical School, Harvard University; Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA.

¹⁵Department of Bioengineering, Department of Electrical Engineering and Computer Science, University of California, Berkeley, CA, USA.

¹⁶Department of Biophysics, Institute of Quantum Biophysics, Sungkyunkwan University, Suwon, Korea.

¹⁷Department of Chemistry and Nanoscience, Ewha Womans University, Seoul, Korea.

¹⁸These authors contributed equally: Md. Mofizur Rahman, Jing Wang, Guosheng Wang.

Corresponding authors : Correspondence to Lixue Wang, Luke P. Lee or Yuan Wan.

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.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-02-21)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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