RSC Advances
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2018
·Vol. 8
·期 11
·6053-6062
·
IF 2.936
Tian-Ying Luo,Xi He,Ji Zhang,Ping Chen,Yan-Hong Liu,Hai-Jiao Wang,Xiao-Qi Yu
Carbon dots (CDs) are photoluminescent nanoparticles with distinctive properties, having great potential in nano-biomaterial systems such as gene/drug delivery vectors and cell imaging agents. Fluorine-doped CD C-6F was prepared by a one-step ring-opening polymerization-dehydrative carbonization (RPDC) approach based on low molecular weight polyethyleneimine (PEI, 600 Da) and fluorinated diglycidyl ethers, while the non-fluorinated counterpart C-6H and the CD prepared from PEI 600 Da solely (C-600) were also prepared for comparison. TEM, FT-IR and XPS were performed to determine the compositions and surface states of the CDs. In vitro cell experiment results reveal that the CDs prepared from RPDC approach have much higher transfection efficiency and cellular uptake than PEI 600 contrasts in various cell lines. Compared to non-fluorinated C-6H, C-6F exhibited distinctly higher transfection efficiency, and up to 30 and 260 times higher efficiency than PEI 25 kDa could be achieved in the absence and presence of serum, respectively, indicating the advantage of F-doping. Besides, these CDs exhibit good cell imaging capability under single wavelength excitation, making the materials suitable for cellular tracking and transfection mechanism studies. These results demonstrate that fluorine-doping is an efficient approach to obtained CD gene vectors with high efficiency and serum tolerance.
研究领域:
生物材料
·
纳米医学
·
细胞生物学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 39
·7963-7973
·
IF 4.543
Y. N. Zhao,Y. Z. Piao,C. M. Zhang,Y. M. Jiang,A. Liu,S. H. Cui,D. F. Zhi,Y. H. Zhen,S. B. Zhang
Headgroups in cationic lipids play very important roles in determining transfection efficiency and toxicity in gene delivery. To better understand the influence of headgroups on gene delivery, a tri-peptide-based lipid was synthesized, wherein the usual quaternary ammonium was replaced by a tri-peptide. Though both the tri-peptide-based lipid (DAO3) and the quaternary ammonium-based lipid (DDCTMA) successfully mediated gene transfection, DAO3 was superior to DDCTMA in both in vitro and in vivo studies. Following their preparation into liposomes, the particle size, zeta potential, and DNA-binding capacity of the liposomes and lipoplexes were characterized to evaluate the efficiency of DAO3 compared to DDCTMA with regard to gene interactions. The expression of luciferase from pDNA mediated by DAO3 was 2-fold greater than than that with DDCTMA in Hep-2 cells, and DAO3/siRNA lipoplexes could silence about 60% luciferase in A549 cancer cells expressing firefly luciferase. DAO3/Luc-siRNA treatment exhibited 3-fold the efficiency of DDCTMA/Luc-siRNA in terms of in vivo luciferase RNAi with the bare density ratio of 0.54 at 48 h. Furthermore, DAO3 could mediate IGF-1R siRNA to inhibit tumor growth through silencing the expression of the IGF-1R protein, whereas DDCTMA showed nearly no effects. Most importantly, DAO3 had no obvious toxicity in vitro and in vivo, due to the biocompatibility of the peptide headgroups. In conclusion, these results demonstrated that the replacement of the quaternary ammonium headgroup by tri-ornithine may increase transfection efficiency and decrease toxicity.
研究领域:
分子生物学
·
基因治疗
·
药物递送
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2019
·
IF 3.829
Jiu Wang,Yajing Wang,Ziqiang Wang,Fan Wang,Jie He,Xiaoyun Yang,Weidong Xie,Ying Liu,Yaou Zhang
The present study aims at designing a thermosensitive gel prepared from w1/o/w2 multiple microemulsions (MMEs) for the vaginal delivery of siRNA. The w1/o/w2 MMEs were prepared by two-step emulsifications: the first step was to prepare primary emulsions (w1/o) by low energy emulsification (LEE); the second step was to obtain stable w1/o/w2 MMEs by self-emulsifying. An extensive formulation optimization process was undertaken. The final w1/o/w2 MMEs could be formed in ddH2O, phosphate buffer solution (PBS, pH 7.4) and 1640 culture media with diameter size about 166.5 ± 13.1, 271.0 ± 11.1 and 278.7 ± 12.1 nm respectively. The release rates of siRNA from solutions, MMEs and MMEs-gels were completed within 2 h, 6 h and13 h respectively. The transfection efficiency of MMEs was confirmed both in vitro and in vivo. The relative target gene expressions of MMEs were 0.07 ± 0.05% vs. 0.37 ± 0.06% in Hela cells against Lipofectamine2000® and 1.88% ± 0.00% vs. 9.65% ± 0.02% in mouse vaginal mucosa against PEI. Good biocompatibility of MMEs was verified by cytotoxicity and pathological studies. Overall, our results indicated the potential of the MMEs-gel system for the vaginal delivery of siRNA.
研究领域:
药剂学
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生物医学工程
·
分子生物学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 7
·1482-1497
·
IF 4.543
Xiaobing Chen,Jun Yang,Hong Liang,Qian Jiang,Bowen Ke,Yu Nie
Integrating the advantages of artificial vectors with bioinspired strategies has opened interesting perspectives in the design of gene delivery systems. Herein, disulfide modified, self-assembled lipopeptides with arginine-rich periphery are demonstrated as gene vectors (RLS). It is surprising that these carriers achieved excellent gene transfection efficacy (up to 380-fold higher than PEI) in different cell lines (HeLa and B16 cells) at relatively low N/P (∼10) ratios, compared to the analog lipopeptides without disulfide bonds (RL, N/P 40). As shown from the morphologies observed by transmission electronic microscopy and surface charge detection by dynamic light scattering, the existence of disulfide bonds may influence the configuration/conformation of the RLS assembly with decreased zeta potential (+27.2 mV), compared to that of the analogs, RL (+46.5 mV). Correspondingly, RLS/DNA complexes showed relatively lower zeta potentials than those of RL/DNA complexes at different N/P ratios. Under the transfection conditions, RLS/DNA complexes (N/P 10) showed even less cellular uptake than that of RL/DNA complexes (N/P 40), and no difference was detected in buffering effect and endosomal escape between RLS and RL complexes. Examination by gel electrophoresis and fluorescence resonance energy transfer (FRET) images in cell culture conditions confirmed that RLS lipoplexes could effectively liberate DNA. Thus, the higher gene transfection efficiency of disulfide modified vectors might be mainly attributed to the cleavage of disulfide bonds; the rapid release of DNA and the superiority of the design was closely related to the reductive conditions in the cells.
研究领域:
生物化学
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分子生物学
·
药物递送
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2011
·
IF 7.164
Congxin Li,Tianying Guo,Dezhong Zhou,Yuling Hu,Hao Zhou,Shufang Wang,Jiatong Chen,Zhengpu Zhang
A novel non-viral gene vector based on poly[poly(ethylene glycol) methacrylate] (PMPEG) and l -glutathione (GSH) grafted chitosan (CS) has been fabricated. First, well-defined brush-like PMPEG living polymers with dithioester residues were prepared by the reversible addition–fragmentation chain transfer (RAFT) polymerization and grafted onto the allylchitosan via radical coupling method. Then, the tripeptide GSH was introduced onto the end of PMPEG chain to give a CS–PMPEG–GSH conjugate. In comparison with pristine chitosan, CS–PMPEG–GSH conjugate could not only condense plasmid DNA (pDNA) and prevent the condensed CS–PMPEG–GSH/pDNA nanoparticle self-aggregation, but also increase the binding ability to cell membrane efficiently and improve decondensed ability of pDNA from the nanoparticles in cytoplasm which thus has resulted in the higher transfection efficiency in mouse embryonic fibroblast cells (NIH3T3). In addition, cytotoxicity assays showed that the conjugate is less cytotoxic than CS, and still retain the cationic polyelectrolyte characteristic as chitosan. These results indicate that the non-viral vector is a promising candidate for gene therapy in clinical application.
研究领域:
生物材料学
·
分子生物学
·
基因治疗
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2012
·
IF 5.479
Xiaojun Cai,Chunyan Dong,Haiqing Dong,Gangmin Wang,Giovanni M. Pauletti,Xiaojing Pan,Huiyun Wen,Isaac Mehl,Yongyong Li,Donglu Shi
A dual stimulus-responsive mPEG-SS-PLL15-glutaraldehyde star (mPEG-SS-PLL15-star) catiomer is developed and biologically evaluated. The catiomer system combines redox-sensitive removal of an external PEG shell with acid-induced escape from the endosomal compartment. The design rationale for PEG shell removal is to augment intracellular uptake of mPEG-SS-PLL15-star/DNA complexes in the presence of tumor-relevant glutathione (GSH) concentration, while the acid-induced dissociation is to accelerate the release of genetic payload following successful internalization into targeted cells. Size alterations of complexes in the presence of 10 mM GSH suggest stimulus-induced shedding of external PEG layers under redox conditions that intracellularly present in the tumor microenvironment. Dynamic laser light scattering experiments under endosomal pH conditions show rapid destabilization of mPEG-SS-PLL15-star/DNA complexes that is followed by facilitating efficient release of encapsulated DNA, as demonstrated by agarose gel electrophoresis. Biological efficacy assessment using pEGFP-C1 plasmid DNA encoding green fluorescence protein and pGL-3 plasmid DNA encoding luciferase as reporter genes indicate comparable transfection efficiency of 293T cells of the catiomer with a conventional polyethyleneimine (bPEI-25k)-based gene delivery system. These experimental results show that mPEG-SS-PLL15-star represents a promising design for future nonviral gene delivery applications with high DNA binding ability, low cytotoxicity, and high transfection efficiency.
研究领域:
生物医学工程
·
分子生物学
·
药剂学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2014
·
IF 8.312
Mingming Wang,Yiyun Cheng
Dendrimers have shown great promise in the design of high efficient and low cytotoxic gene vectors . In this study, we synthesized a list of fluorobenzoic acid-modified dendrimers by a facile synthetic route and explored their potential applications as non-viral gene vectors. Fluorination on the aromatic rings significantly improves the transfection efficacy of benzoic acid-modified dendrimers. The transfection efficacy increases with increasing number of fluorine atoms on the aromatic rings of the conjugated benzoic acid . The most efficient conjugate shows superior efficacy to polymer-based commercial reagents such as SuperFect and PolyFect, and comparable efficacy to lipid-based commercial reagents such as Lipofectamine 2000. In addition, the fluorobenzoic acid-modified dendrimers show low cytotoxicity on the transfected cells. The improved transfection efficacy of fluorobenzoic acid-modified dendrimers is due to enhanced cellular uptake and/or easier DNA unpacking behavior compared to non-modified dendrimers. These results provide a new fluorination strategy to generate a library of highly efficient and non-cytotoxic polymeric gene vectors.
研究领域:
生物化学
·
分子生物学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCES IN POLYMER TECHNOLOGY
·
2021
·
IF 2.389
Lin Lin,Jie Chen,Yingying Hu,Huapan Fang,Kui Wang,Huayu Tian,Xuesi Chen
Polyethyleneimine (PEI) has been extensively used as a common gene carrier due to its high gene transfection efficiency. PEI1.8k shows significantly lower cytotoxicity than its high molecular weight counterparts. However, it also has the problem of low gene transfection efficiency. To address the dilemma, a highly effective crosslinker (DTME) was synthesized to react with PEI1.8k to obtain CS-PEI1.8k. The reaction showed several advantages, such as a fast process in room temperature within nine hours with the product which can directly complex with DNA after removing the solvent. The ability of CS-PEI1.8k to agglomerate with DNA was proven by particle size, zeta potential, and gel retardation assays. The cytotoxic in vitro transfection ability and cell internalization capacity of CS-PEI1.8k were tested to verify the transfection capacity of CS-PEI1.8k. Moreover, we also studied the mechanism of the relatively high level of gene transfection by this binary complex compared with PEI25k.
研究领域:
分子生物学
·
基因治疗
·
药物递送
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Polymer Materials
·
2025
·
IF 4.7
Shanshan Xiao,Ning Li,Shaobo Feng,Ziyuan Song
Cationic polymers are widely studied as gene delivery carriers due to their low immunogenicity and facile structural modulation. The hydrophobic modification of cationic polymers is an effective strategy to optimize the transfection efficiency. However, the fine-tuning of the hydrophobic–hydrophilic balance to improve the transfection remains largely unexplored. In this article, we reported the enhanced performance of poly(l-lysine) (PLL), one of the first polymeric gene vectors with low potency, through the incorporation and modulation of hydrophobic blocks. Both the fraction and the distribution of hydrophobic blocks were critical, which influenced the condensation of DNA and the internalization of polyplexes. With proper hydrophobicity design, the multiblock copolypeptide exhibited 2–3 orders of magnitude higher transfection efficiency than its PLL analogue, mediating effective intracellular delivery of the p53 gene to inhibit the growth of tumor cells. This study highlights hydrophobic modification to boost the potency of cationic polymers, providing insights into the control over the hydrophobic–hydrophilic balance in the design of polymeric gene vectors.
研究领域:
生物材料学
·
基因治疗
·
分子生物学
✓ 已验证
DOI
高影响因子
REACTIVE & FUNCTIONAL POLYMERS
·
2025
·
IF 5.1
Ting Ju,Fangyuan Duan,Jiayu Wang,Yishu Yin,Weihong Lu
For gene delivery, cationic polymers must balance two crucial parameters: transfection efficiency and cytotoxicity. Although PEI remains a widely used gene vector, its clinical translation has been hindered by significant toxicity concerns. In this study, three low-molecular-weight PEI derivatives modified with oligosaccharides, trehalose, raffinose, and stachyose, are referred to as TRON-PEI, RAON-PEI, and STON-PEI, respectively. The potential of these polymers as safe gene delivery systems was explored and the influence of oligosaccharide modifications on the transfection efficiency of PEI-based vectors was examined. The physicochemical properties of the three PEI variants, including their ability to bind pDNA, cytotoxicity, zeta potential, and complex size, were analyzed. The experimental results revealed that oligosaccharide-modified PEI polymers effectively condensed pDNA into nanoparticles with diameters ranging from 106 to 142 nm. Among these variants, RAON-PEI-3 and TRON-PEI-3 exhibited optimal performance, achieving high transfection efficiency with minimal cytotoxicity across multiple cell lines (HeLa, MHCC-97H, and HepG2). Cellular co -localization and molecular docking assays demonstrated that the three vectors could successfully bind to pDNA and that the three polymers were able to target receptor proteins (ASGP-R and galectin-2) on the membrane surface of cancer cells. In addition, the cellular co-localization assay successfully verified that RAON-PEI-3 and TRON-PEI-3 were capable of rapid lysosomal escape and mitochondrial targeting. When complexed with the p53 plasmid, these vectors successfully mediated tumor cell apoptosis, as confirmed by western blotting and live/dead assays. Our results demonstrated that oligosaccharide modification represents a promising strategy for developing PEI-based gene delivery systems with enhanced safety profiles and therapeutic potential.
研究领域:
分子生物学
·
药剂学
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
LANGMUIR
·
2018
·
IF 3.789
Shengran Li,Binggang Chen,Yangchun Qu,Xinxin Yan,Wenliang Wang,Xiaojing Ma,Bo Wang,Sanrong Liu,Xifei Yu
As one of the most promising therapeutic methods, gene therapy has been playing a more and more important role in treating disease due to its ultra-high therapy efficiency. Even if nonviral gene vectors represented by polycation, liposomal, dendrimers, and zwitterionic materials have made great progress in gene complexation, low immunogenicity, and biocompatibility, intracellular gene release with low toxicity is effectively still a bottleneck restricting the clinical application of gene therapy. We designed and synthesized a reactive oxygen species (ROS)-responsive dendrimer poly(amido amine)-N-(4-boronobenzyl)-N,N-diethyl-2-(propionyloxy)ethan-1-aminium (PAMAM-(B-DEAEP)16) as a gene vector whose potential can vary from positive to negative under the elevated ROS (H2O2) in cancerous cells. Dynamic light scattering results showed that the zeta potential of PAMAM-(B-DEAEP)16 decreased from +12.3 to −5 mV under 80 mM H2O2 in PBS buffer. The 1H NMR results demonstrated that the intermediate status of PAMAM-(B-DEAEP)16 was zwitterionic in ∼6 h because it consisted of the positive quaternary ammonium and negative carboxylic acid simultaneously before the ester bond was completely hydrolyzed. Gel retardation assay showed that PAMAM-(B-DEAEP)16 can condense DNA at above N/P = 1; then, PAMAM-(B-DEAEP)16 transfers to zwitterionic, which begins to continuously release DNA with the decrease in the positive charges and increase in the negative charges, and finally to negatively charged poly(amido amine)-propionic acid (PAMAM-PAc16) in the 80 mM H2O2. Fluorescence-labeled Cy-5 DNA indicated that PAMAM-(B-DEAEP)16 can enter into the cell completely in ∼4 h. The results showed that this compound we designed exhibited higher gene transfection efficiency and lower cytotoxicity than commercial PEI. This is the first time that the positively charged dendrimer was transferred to zwitterionic dendrimer under the stimuli of H2O2 and was successfully applied to gene delivery. Unlike all of the previous reports, we did not seek a compromise between the high gene transfection and low toxicity but find a new avenue to make the gene carrier not only have higher gene transfection efficiency but also exhibit lower toxicity by introducing stimuli-sensitive groups into the positively charged dendrimer to make it capable of adjusting the charge property according to the microenvironment. This study not only provides a good method to design materials for gene delivery but also opens a new perspective to understand the process of gene delivery.
研究领域:
生物医学工程
·
基因治疗
·
材料科学
✓ 已验证
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
Aijie Guo,Yun Wang,Shaohui Xu,Xiao Zhang,Min Li,Qing Liu,Yuanyuan Shen,Derong Cui,Shengrong Guo
Because the surface of the cationic polymer gene complex is positively charged, it can result in problems such as poor blood stability and cytotoxicity. Therefore, reducing the positive charge of the cationic gene complex without affecting its transfection efficiency is crucial. To achieve this objective, a pH -responsive charge-convertible ternary complex was developed in this study. Modified plyethylenimine (PEI) with two different degrees of substitution of NH 2 (plyethylenimine-1,2-cyclohexanedicarboxylic anhydride, PEI-CCA, and folic acid-plyethylenimine-1,2-cyclohexanedicarboxylic anhydride, FA-PEI-CCA) were first obtained by a chemical graft reaction. PEI-CCA and FA-PEI-CCA have significantly lower cytotoxicities and much better blood compatibilities than PEI does, and the former have an undifferentiated compression capability of DNA . The zeta potential values of the as-prepared ternary complexes (PEI-CCA/PEI/DNA and FA-PEI-CCA/PEI/DNA) were negative at pH 7.4 and positive at pH 6.5, with particle sizes of approximately 150 nm. MTT assays demonstrated the significantly lower cytotoxicities of the ternary complexes compared to that of PEI/DNA. Moreover, the cytotoxicities of the ternary complexes were lower at pH 7.4 than pH 6.5. Transfection experiments in vitro revealed that the mean fluorescence intensities and transfection efficiencies of the ternary complexes were lower than for PEI/DNA at pH 7.4 but were almost the same at pH 6.5. The ternary complex with a FA group had significantly higher mean fluorescence intensity and transfection efficiency than did the ternary complex without it. In addition, the transfection experiment in 293T cells preliminarily validated the targeting function of the FA group of the ternary complex.
研究领域:
分子生物学
·
基因治疗
·
药物递送
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）