Nucleic acid-based therapies hold promise for treating previously intractable diseases but require effective delivery vectors to protect the therapeutic agents and ensure efficient transfection. Cationic polymeric vectors are particularly notable for their adaptability, high transfection efficiency, and low cost, but their positive charge often attracts blood proteins, causing aggregation and reduced transfection efficiency. Addressing this, we designed an anionic peptide-grafted dextran (Dex-LipE5H) to serve as a cross-linkable coating to bolster the stability of cationic polymer/nucleic acid complexes. The Dex-LipE5H was synthesized through a Michael addition reaction, combining an anionic peptide (LipE5H) with dextran modified by divinyl sulfone. We demonstrated Dex-lipE5H utility in a novel ternary nucleic acid delivery system, CDex-LipE5H/PEI/nucleic acid. CDex-LipE5H/PEI/nucleic acid demonstrated lower cytotoxicity and superior anti-protein absorption ability compared to PEI/pDNA and Dex-LipE5H/PEI/pDNA. Most notably, the crosslinked CDex-LipE5H/PEI/pDNA demonstrated remarkable transfection performance in HepG2 cells, which poses significant transfection challenges, even in a medium with 20% serum. This system’s effective siRNA interference performance was further validated through a PCSK9 gene knockdown assay. This investigation provides novel insights and contributes to the design of cost-effective, next-generation nucleic acid delivery systems with enhanced blood stability and transfection efficiency.
Skip Nav Destination
Elevating nucleic acid delivery via a stable anionic peptide-dextran ternary system
Article navigation
September 2023
Research Article|
October 04 2023
Elevating nucleic acid delivery via a stable anionic peptide-dextran ternary system
Alex Cheng
;
Alex Cheng
(Conceptualization, Formal analysis, Software, Writing – original draft, Writing – review & editing)
1
Department of Chemical Engineering, University of Illinois at Chicago
, Chicago, Illinois 60607
Search for other works by this author on:
Ying Liu
;
Ying Liu
(Resources, Supervision, Writing – review & editing)
1
Department of Chemical Engineering, University of Illinois at Chicago
, Chicago, Illinois 60607
Search for other works by this author on:
Hai-Qing Song
Hai-Qing Song
a)
(Conceptualization, Data curation, Formal analysis, Methodology, Software, Supervision, Validation, Writing – original draft, Writing – review & editing)
1
Department of Chemical Engineering, University of Illinois at Chicago
, Chicago, Illinois 606072
Engineering Research Center of Clinical Functional Materials and Diagnosis and Treatment Devices of Zhejiang Province, Wenzhou Institute, University of Chinese Academy of Sciences
, Wenzhou, Zhejiang 325000, China
a)Author to whom correspondence should be addressed: hqsong89@163.com
Search for other works by this author on:
a)Author to whom correspondence should be addressed: hqsong89@163.com
Biointerphases 18, 051001 (2023)
Article history
Received:
August 22 2023
Accepted:
September 12 2023
Citation
Alex Cheng, Ying Liu, Hai-Qing Song; Elevating nucleic acid delivery via a stable anionic peptide-dextran ternary system. Biointerphases 1 September 2023; 18 (5): 051001. https://doi.org/10.1116/6.0003084
Download citation file:
Sign in
Don't already have an account? Register
Sign In
You could not be signed in. Please check your credentials and make sure you have an active account and try again.
Sign in via your Institution
Sign in via your InstitutionPay-Per-View Access
$40.00
95
Views