Polyelectrolyte-coated liposomes microfluidically assembled in one-step for enhancing cell endocytosis and in-vivo immune responses

Xin-An Chen; Chuan-Chang Chuang; Cheng-Cheung Chen; Chia-Ying Lee; Chia-Ying Chin; Jenn-Jong Young; Meng-Yi Bai; Chuan-Chung Chuang

doi:10.1016/j.colsurfb.2024.114030

Polyelectrolyte-coated liposomes microfluidically assembled in one-step for enhancing cell endocytosis and in-vivo immune responses

Colloids Surf B Biointerfaces. 2024 Sep:241:114030. doi: 10.1016/j.colsurfb.2024.114030. Epub 2024 Jun 14.

Authors

Xin-An Chen¹, Chuan-Chang Chuang², Cheng-Cheung Chen³, Chia-Ying Lee⁴, Chia-Ying Chin⁴, Jenn-Jong Young⁵, Meng-Yi Bai⁶, Chuan-Chung Chuang⁷

Affiliations

¹ Biomedical Engineering Program, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei City 10607, Taiwan, ROC.
² Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC; Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei City 11490, Taiwan, ROC.
³ Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC; Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei City 11490, Taiwan, ROC.
⁴ Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC.
⁵ Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 23742, Taiwan, ROC. Electronic address: [email protected].
⁶ Biomedical Engineering Program, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei City 10607, Taiwan, ROC; Adjunct Appointment to the Department of Biomedical Engineering, National Defense Medical Center, Taipei City 11490, Taiwan, ROC. Electronic address: [email protected].
⁷ School of Dentistry and Graduate Institute of Dental Science, National Defense Medical Center, Taipei City 11490, Taiwan, ROC; Department of dentistry, Tri-Service General Hospital, Taipei City 11490, Taiwan, ROC. Electronic address: [email protected].

PMID: 38901267
DOI: 10.1016/j.colsurfb.2024.114030

Abstract

To enhance the cellular uptake of liposomes, we prepared conventional liposomes with targeting molecules and surface-charged liposomes and evaluated their potential as nano-carriers and vaccine adjuvants by comparing their endocytosis efficiencies using immune cells. Surface-charged liposomes were synthesized via a one-step microfluidic method, which provided a novel, simple, fast, and highly reproducible method for preparing liposomes. Flow cytometry revealed that cationic polyelectrolyte-coated liposomes exhibited higher endocytosis efficiencies (of up to a factor of 100) in A774A.1 cells and JAWs II cells compared with uncoated liposomes or those coated with anionic polyelectrolytes. Positively charged liposomes exhibited some cytotoxicity at quaternary-chitosan coating concentrations higher than 6 mg/mL; however, significantly lower cytotoxicities (by a factor of almost ten) were obtained by protein mixing. Furthermore, BALB/c mice vaccinated with a mixture of Anthrax vaccine adsorbed (AVA) and quaternary chitosan-coated liposomes showed faster and stronger anti-PA IgG inductions compared to those vaccinated with AVA alone, with titers positively correlating with the amount of cationic liposome used. This finding clearly reveals that quaternary chitosan-coated liposomes act as both nano-carriers and vaccine adjuvants that significantly enhance in-vivo immune responses to vaccines with low immunogenicities.

Keywords: Anthrax vaccine; Cytotoxicity; Endocytosis; One-step microfluidic synthesis; Polyelectrolyte-coated liposomes.

MeSH terms

Animals
Chitosan / chemistry
Endocytosis* / drug effects
Female
Liposomes* / chemistry
Mice
Mice, Inbred BALB C*
Microfluidics / methods
Polyelectrolytes / chemistry

Substances

Liposomes
Polyelectrolytes
Chitosan