Spermine Significantly Increases the Transfection Efficiency of Cationic Polymeric Gene Vectors

<b>Background/Objectives:</b> Non-viral vectors have gained recognition for their ability to enhance the safety of gene delivery processes. Among these, polyethyleneimine (PEI) stands out as the most widely utilized cationic polymer due to its accessibility. Traditional methods of modify...

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Main Authors: Yue Lv, Jiaoqin Xue, Pengfei Cui, Lin Qiu
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/17/1/131
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author Yue Lv
Jiaoqin Xue
Pengfei Cui
Lin Qiu
author_facet Yue Lv
Jiaoqin Xue
Pengfei Cui
Lin Qiu
author_sort Yue Lv
collection DOAJ
description <b>Background/Objectives:</b> Non-viral vectors have gained recognition for their ability to enhance the safety of gene delivery processes. Among these, polyethyleneimine (PEI) stands out as the most widely utilized cationic polymer due to its accessibility. Traditional methods of modifying PEI, such as ligand conjugation, chemical derivatization, and cross-linking, are associated with intricate preparation procedures, limited transfection efficiency, and suboptimal biocompatibility. <b>Methods:</b> In this investigation, enhanced transfection efficiency was achieved through the straightforward physical blending of PEI carriers with spermine. <b>Results:</b> Transfection assays explored the maximal enhancement potential conferred by spermine, alongside further methodological refinements aimed at optimizing transfection efficacy, showcasing a potential increase of up to 40.7%. Through the comparison of different addition sequences of spermine, the optimal complex PEI/Spermine/DNA for transfection efficiency was selected. Characterization of PEI/Spermine/DNA revealed that, compared to PEI/DNA, its particle size increased to approximately 150 nm. Molecular dynamics simulation results revealed that spermine can enhance the interaction between PEI and DNA, thereby forming a system with lower energy and greater stability. Mechanistic inquiries studies also disclosed that spermine augments the endosomal escape capability of PEI carriers without altering pathways involved in the cellular uptake of gene nanoparticles, thereby facilitating heightened gene expression. <b>Conclusions:</b> PEI-Sper emerges as a promising non-viral vector for gene delivery, distinguished by its simplicity in preparation, cost-effectiveness, and superior transfection efficiency.
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institution Kabale University
issn 1999-4923
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publishDate 2025-01-01
publisher MDPI AG
record_format Article
series Pharmaceutics
spelling doaj-art-911e6eeea60346179854be8c91a85dcb2025-01-24T13:46:05ZengMDPI AGPharmaceutics1999-49232025-01-0117113110.3390/pharmaceutics17010131Spermine Significantly Increases the Transfection Efficiency of Cationic Polymeric Gene VectorsYue Lv0Jiaoqin Xue1Pengfei Cui2Lin Qiu3School of Pharmacy, Changzhou University, Changzhou 213164, ChinaSchool of Pharmacy, Changzhou University, Changzhou 213164, ChinaSchool of Pharmacy, Changzhou University, Changzhou 213164, ChinaSchool of Pharmacy, Changzhou University, Changzhou 213164, China<b>Background/Objectives:</b> Non-viral vectors have gained recognition for their ability to enhance the safety of gene delivery processes. Among these, polyethyleneimine (PEI) stands out as the most widely utilized cationic polymer due to its accessibility. Traditional methods of modifying PEI, such as ligand conjugation, chemical derivatization, and cross-linking, are associated with intricate preparation procedures, limited transfection efficiency, and suboptimal biocompatibility. <b>Methods:</b> In this investigation, enhanced transfection efficiency was achieved through the straightforward physical blending of PEI carriers with spermine. <b>Results:</b> Transfection assays explored the maximal enhancement potential conferred by spermine, alongside further methodological refinements aimed at optimizing transfection efficacy, showcasing a potential increase of up to 40.7%. Through the comparison of different addition sequences of spermine, the optimal complex PEI/Spermine/DNA for transfection efficiency was selected. Characterization of PEI/Spermine/DNA revealed that, compared to PEI/DNA, its particle size increased to approximately 150 nm. Molecular dynamics simulation results revealed that spermine can enhance the interaction between PEI and DNA, thereby forming a system with lower energy and greater stability. Mechanistic inquiries studies also disclosed that spermine augments the endosomal escape capability of PEI carriers without altering pathways involved in the cellular uptake of gene nanoparticles, thereby facilitating heightened gene expression. <b>Conclusions:</b> PEI-Sper emerges as a promising non-viral vector for gene delivery, distinguished by its simplicity in preparation, cost-effectiveness, and superior transfection efficiency.https://www.mdpi.com/1999-4923/17/1/131polyethyleneiminesperminetransfection efficiencyendosome escape
spellingShingle Yue Lv
Jiaoqin Xue
Pengfei Cui
Lin Qiu
Spermine Significantly Increases the Transfection Efficiency of Cationic Polymeric Gene Vectors
Pharmaceutics
polyethyleneimine
spermine
transfection efficiency
endosome escape
title Spermine Significantly Increases the Transfection Efficiency of Cationic Polymeric Gene Vectors
title_full Spermine Significantly Increases the Transfection Efficiency of Cationic Polymeric Gene Vectors
title_fullStr Spermine Significantly Increases the Transfection Efficiency of Cationic Polymeric Gene Vectors
title_full_unstemmed Spermine Significantly Increases the Transfection Efficiency of Cationic Polymeric Gene Vectors
title_short Spermine Significantly Increases the Transfection Efficiency of Cationic Polymeric Gene Vectors
title_sort spermine significantly increases the transfection efficiency of cationic polymeric gene vectors
topic polyethyleneimine
spermine
transfection efficiency
endosome escape
url https://www.mdpi.com/1999-4923/17/1/131
work_keys_str_mv AT yuelv sperminesignificantlyincreasesthetransfectionefficiencyofcationicpolymericgenevectors
AT jiaoqinxue sperminesignificantlyincreasesthetransfectionefficiencyofcationicpolymericgenevectors
AT pengfeicui sperminesignificantlyincreasesthetransfectionefficiencyofcationicpolymericgenevectors
AT linqiu sperminesignificantlyincreasesthetransfectionefficiencyofcationicpolymericgenevectors