Cyclic poly(β-amino ester)s with enhanced gene transfection activity synthesized through intra-molecular cyclization

Wang, Chenfei; Huang, Xiaobei; Sun, Litao; Li, Qiuxia; Li, Zhili; Yong, Haiyang; Che, Delu; Yan, Cong; Geng, Songmei; Wang, Wenxin; Zhou, Dezhong

doi:10.1039/d1cc06480k

Cited by 18 publications

(16 citation statements)

References 22 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It should be noted that the condensation ability has been shown to have a critical role in transfection efficiency, which has been studied in several investigations [ 21 , 45 , 46 , 47 ]. On the one hand, the interaction between the polymer and nucleic acid materials is necessary for polyplex formation, protection against enzymatic digestion, and cell entry via adsorptive endocytosis.…”

Section: Resultsmentioning

confidence: 99%

Interleukin-12 Plasmid DNA Delivery by N-[(2-Hydroxy-3-trimethylammonium)propyl]chitosan-Based Nanoparticles

et al. 2022

View full text Add to dashboard Cite

Cationic polysaccharides are capable of forming polyplexes with nucleic acids and are considered promising polymeric gene carriers. The objective of this study was to evaluate the transfection efficiency and cytotoxicity of N-[(2-hydroxy-3-trimethylammonium)propyl] chitosan salt (HTCS), a quaternary ammonium derivative of chitosan (CS), which benefits from non-ionizable positive charges. In this work, HTCS with a full quaternization of amino groups and a molar mass of 130,000 g·mol−1 was synthesized to use for delivery of a plasmid encoding the interleukin-12 (IL-12) gene. Thus, a polyplex based on HTCS and the IL-12 plasmid was prepared and then was characterized in terms of particle size, zeta potential, plasmid condensation ability, and protection of the plasmid against enzymatic degradation. We showed that HTCS was able to condense the IL-12 plasmid by the formation of polyplexes in the range of 74.5 ± 0.75 nm. The level of hIL-12 production following the transfection of the cells with HTCS polyplexes at a C/P ratio of 8:1 was around 4.8- and 2.2-fold higher than with CS and polyethylenimine polyplexes, respectively. These findings highlight the role of HTCS in the formation of polyplexes for the efficient delivery of plasmid DNA.

show abstract

Section: Resultsmentioning

confidence: 99%

Interleukin-12 Plasmid DNA Delivery by N-[(2-Hydroxy-3-trimethylammonium)propyl]chitosan-Based Nanoparticles

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Previous research has demonstrated that polymers with a cyclic structure often display better biocompatibility and DNA encapsulation capabilities than those with a linear or branched structure. 12,14,15 Herein, we report the first successful construction of a series of cyclic poly(β-amino ester)s (CPAEs) with different types of ring structures by regulating the cyclization tendency at different stages of the step-growth polymerization (SGP).…”

Section: ■ Introductionmentioning

confidence: 99%

3D Macrocyclic Structure Boosted Gene Delivery: Multi-Cyclic Poly(β-Amino Ester)s from Step Growth Polymerization

Wang

et al. 2023

J. Am. Chem. Soc.

Self Cite

View full text Add to dashboard Cite

The topological structures of polymers play a critical role in determining their gene delivery efficiency. Exploring novel polymeric structures as gene delivery vectors is thus of great interest. In this work, a new generation of multi-cyclic poly(β-amino ester)s (CPAEs) with unique topology structure was synthesized for the first time via step growth polymerization. Through controlling the occurrence stage of cyclization, three types of CPAEs with rings of different sizes and topologies were obtained. In vitro experiments demonstrated that the CPAEs with macro rings (MCPAEs) significantly boosted the transgene expression comparing to their branched counterparts. Moreover, the MCPAE vector with optimized terminal group efficiently delivered the CRISPR plasmid coding both Staphylococcus aureus Cas9 nuclease and dual guide sgRNAs for gene editing therapy.

show abstract

“…By changing the end-modified groups, the transfection performance can be improved by several magnitude orders. Then in 2016, Wang et al constructed hyperbranched PAE (HPAE) via the facile A2 + B3 + C2 Michael addition strategy with amines and vinyl groups [ 9 , 10 ], which further improved the gene transfection performance of PAE vectors by increasing the optimal terminal group amount [ 9 , 11 , 12 , 13 , 14 ]. Despite years of research on HPAE structural factors, such as molecular weight, branch ratio, and terminal group screening [ 15 , 16 , 17 , 18 ], there is still a long pathway to clinical applications.…”

Section: Introductionmentioning

confidence: 99%

Hyperbranched Poly(β-amino ester)s (HPAEs) Structure Optimisation for Enhanced Gene Delivery: Non-Ideal Termination Elimination

Lyu

et al. 2022

Nanomaterials

Self Cite

View full text Add to dashboard Cite

Many polymeric gene delivery nano-vectors with hyperbranched structures have been demonstrated to be superior to their linear counterparts. The higher delivery efficacy is commonly attributed to the abundant terminal groups of branched polymers, which play critical roles in cargo entrapment, material-cell interaction, and endosome escape. Hyperbranched poly(β-amino ester)s (HPAEs) have developed as a class of safe and efficient gene delivery vectors. Although numerous research has been conducted to optimise the HPAE structure for gene delivery, the effect of the secondary amine residue on its backbone monomer, which is considered the non-ideal termination, has never been optimised. In this work, the effect of the non-ideal termination was carefully evaluated. Moreover, a series of HPAEs with only ideal terminations were synthesised by adjusting the backbone synthesis strategy to further explore the merits of hyperbranched structures. The HPAE obtained from modified synthesis methods exhibited more than twice the amounts of the ideal terminal groups compared to the conventional ones, determined by NMR. Their transfection performance enhanced significantly, where the optimal HPAE candidates developed in this study outperformed leading commercial benchmarks for DNA delivery, including Lipofectamine 3000, jetPEI, and jetOPTIMUS.

show abstract

Cyclic poly(β-amino ester)s with enhanced gene transfection activity synthesized through intra-molecular cyclization

Abstract: Topological structure plays a critical role in gene delivery of cationic polymers. Cyclic poly(ß-amino ester)s (CPAEs) are successfully synthesized via sequential Michael addition and free radical initiating ring-closure reaction. CPAE...

Cited by 18 publications

References 22 publications

Interleukin-12 Plasmid DNA Delivery by N-[(2-Hydroxy-3-trimethylammonium)propyl]chitosan-Based Nanoparticles

Interleukin-12 Plasmid DNA Delivery by N-[(2-Hydroxy-3-trimethylammonium)propyl]chitosan-Based Nanoparticles

3D Macrocyclic Structure Boosted Gene Delivery: Multi-Cyclic Poly(β-Amino Ester)s from Step Growth Polymerization

Hyperbranched Poly(β-amino ester)s (HPAEs) Structure Optimisation for Enhanced Gene Delivery: Non-Ideal Termination Elimination

Contact Info

Product

Resources

About