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Preparation and Biological Property Evaluation of Novel Cationic Lipid-Based Liposomes for Efficient Gene Delivery

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Abstract

Novel cationic lipid-based liposomes prepared using an amphiphilic cationic lipid material, N,N-dimethyl-(N′,N′-di-stearoyl-1-ethyl)1,3-diaminopropane (DMSP), have been proposed to enhance the transfection of nucleic acids. Herein, we designed and investigated liposomes prepared using DMSP, soybean phosphatidylcholine, and cholesterol. This novel gene vector has high gene loading capabilities and excellent protection against nuclease degradation. An in vitro study showed that the liposomes had lower toxicity and superior cellular uptake and transfection efficiency compared with Lipofectamine 2000. An endosomal escape study revealed that the liposomes demonstrated high endosomal escape and released their genetic payload in the cytoplasm efficiently. Mechanistic studies indicated that the liposome/nucleic acid complexes entered cells through energy-dependent endocytosis that was mediated by fossa proteins. These results suggest that such cationic lipid-based liposome vectors have potential for clinical gene delivery.

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Acknowledgments

The authors thank the Pharmacy Department, Zhejiang University, Women’s Hospital, School of Medicine and School of Pharmacy, Zhejiang University of Technology, for the instrument support.

Funding

This work was financially supported by the National Natural Science Foundation of China, General Program (Grant Nos. 81802630, 81873838, 81802587) and Public Welfare Technology Research Project of Zhejiang Province (LGF18H300003).

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Authors and Affiliations

  1. Pharmacy Department, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, China

    Yunchun Zhao, Xiaorong Wang, Xiaoling Zheng, Yongquan Zheng, Yue Chen, Weidong Fei & Caihong Zheng

  2. School of Pharmacy, Zhejiang University of Technology, Hangzhou, 310014, China

    Haili Zheng, Jiahuan Zhu & Wenxi Wang

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  1. Yunchun Zhao
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  2. Haili Zheng
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  3. Xiaorong Wang
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  4. Xiaoling Zheng
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  5. Yongquan Zheng
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Correspondence to Wenxi Wang or Caihong Zheng.

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Zhao, Y., Zheng, H., Wang, X. et al. Preparation and Biological Property Evaluation of Novel Cationic Lipid-Based Liposomes for Efficient Gene Delivery. AAPS PharmSciTech 22, 22 (2021). https://doi.org/10.1208/s12249-020-01868-w

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