CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Hongqi Ren,Shuai Liu,Jixiang Yang,Xian Zhang,Hao Zhou,Jiatong Chen,Tianying Guo
A novel non-viral gene carrier based on N , N , N -trimethylchitosan (TMC) has been fabricated. First, well-defined copolymer P (PEGMA- co -DMAEMA) was synthesized through reversible addition fragmentation chain transfer (RAFT) polymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and N , N -(2-dimethylamino)ethyl methacrylamide (DMAEMA). Then allyl group grafting N , N , N -trimethylchitosan (Allyl-TMC) was synthesized via the reaction between allyl bromide and hydroxyl of TMC. Finally, P (PEGMA- co -DMAEMA) and folate were ordinally grafted onto Allyl-TMC to obtain TMC- g - P (PEGMA- co -DMAEMA)-FA. In comparison with pristine chitosan, TMC- g - P (PEGMA- co -DMAEMA)-FA has achieved both better water solubility and stronger pDNA packaging ability, which can contribute to improving gene transfection. Gene delivery efficiency of a series of TMC based functional polymers with different chitosan molecular weights has been tested. The results show that 20k-TMC- g - P (PEGMA- co -DMAEMA)-FA/pDNA complex at the weight ratio of 20 achieve the highest transfection efficiency in 293 T cells. This work presents a new strategy to modify chitosan efficiently as gene carrier material.
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
RSC Advances
·
2021
·Vol. 11
·期 32
·19450-19460
·
IF 3.361
Zhao Wang,Jingjing Sun,Mingrui Li,Ting Luo,Yulin Shen,Amin Cao,Ruilong Sheng
Using natural-based lipids to construct biocompatible, controllable and efficient nanocarriers and elucidating their structure–function relationships, was regarded as an important area for creating sustainable biomaterials. Herein, we utilized two natural steroids: cholesterol and diosgenin (bearing different hydrophobic tails) as the building blocks, to synthesize a series of natural steroid-based cationic random copolymers PMA6Chol-r-PDMAEMA and PMA6Dios-r-PDMAEMA via RAFT polymerization. The results demonstrated that the steroid-r-PDMAEMA copolymers could efficiently bind pDNA (N/P < 3.0) and then form near-spherical shape (142–449 nm) and positively-charged (+11.5 to +19.6 mV) nanoparticles. The in vitro cytotoxicity and gene transfection efficiency greatly depend on the steroid hydrophobic tail structures and steroid/PDMAEMA block ratios. Optimum transfection efficiency of the (Chol-P1/pDNA and Dios-P3/pDNA) nanoplexes could reach to 18.1–31.2% of the PEI-25K/pDNA complex. Moreover, all of the steroid-r-PDMAEMA/Cy3-pDNA nanoplexes have an obvious “lysosome localization” effect, indicating the steroid structures do not remarkably influence the intracellular localization behaviors of these nanoplexes.
研究领域:
生物技术
·
药学
·
材料科学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 10
·2095-2107
·
IF 7
Yu Wei,Ting He,Qunjie Bi,Huan Yang,Xueyi Hu,Rongrong Jin,Hong Liang,Yongqun Zhu,Rongsheng Tong,Yu Nie
The success of mRNA vaccines for COVID-19 prevention raised global awareness of the importance of nucleic acid drugs. The approved systems for nucleic acid delivery were mainly formulations of different lipids, yielding lipid nanoparticles (LNPs) with complex internal structures. Due to the multiple components, the relationship between the structure of each component and the overall biological activity of LNPs is hard to study. However, ionizable lipids have been extensively explored. In contrast to former studies on the optimization of hydrophilic parts in single-component self-assemblies, we report in this study on structural alterations of the hydrophobic segment. We synthesize a library of amphiphilic cationic lipids by varying the lengths (C = 8–18), numbers (N = 2, 4), and unsaturation degrees (Ω = 0, 1) of hydrophobic tails. Notably, all self-assemblies with nucleic acid have significant differences in particle size, stability in serum, membrane fusion, and fluidity. Moreover, the novel mRNA/pDNA formulations are characterized by overall low cytotoxicity, efficient compaction, protection, and release of nucleic acids. We find that the length of hydrophobic tails dominates the formation and stability of the assembly. And at a certain length, the unsaturated hydrophobic tails enhance the membrane fusion and fluidity of assemblies and thus significantly affect the transgene expression, followed by the number of hydrophobic tails.
研究领域:
药学
·
分子生物学
·
纳米技术
·
药物递送系统
·
病毒学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2017
·Vol. 7
·期 1
·1-12
·
IF 4.259
Wang Hongwei,Li Xiaoxi,Chen Ling,Huang Xiaoyi,Li Lin
This study aims at developing biocompatible starch based gene carriers with good gene delivery and transfection efficacy. By controlling the molecular weight and aggregation behavior of spermine modified cationic starch (CS) molecules, nanocomplexes spontaneously formed through electrostatic interaction using CS and plasmid pAcGFP1-C1 (pDNA) displaying different structural changes (particle size, zeta potential, shape, compactness) response to the simulated intracellular pH variation. Results indicated that CS2 with weight average molecular weight ( Mw ) of 6.337 × 10 4 g/mol displayed relatively higher transfection efficacy (~30%) in HepG2 cells than others and revealed significantly low cytotoxicity. By simulating the intracellular pH variation, Dynamic Light Scattering (DLS) and Small Angle X-ray Scattering (SAXS) results demonstrated that CS2 could bind to pDNA tightly and form nanocomplexes with smaller and compact internal aggregate structure at acidic conditions, which facilitated the effective pDNA protection under endosome pH change, while larger and loose internal aggregate structure at physiological pH which promoted the disintegration of CS2/pDNA nanocomplexes. Therefore, CS with suitable Mw of around 6.0 × 10 4 g/mol represents a potential gene carrier for gene delivery. This study also demonstrated that controlling the internal nanostructure change of polymer/gene nanocomplexes could provide guidance in designing effective starch based gene carriers.
研究领域:
生物技术
·
基因治疗
·
材料科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-18
·
IF 12.6
Shen Mingkui,Hou Yan,Xu Shihui,Tan Jun,Zhou Honggang,Miao Qi,Zhang Wanheng,Chen Yazhou,Wang Nana,Wang Yongtao
Biochips are widely applied to manipulate the geometrical morphology of stem cells in recent years. Patterned antenna-like pseudopodia are also probed to explore the influence of pseudopodia formation on gene delivery and expression on biochips. However, how the antenna-like pseudopodia affect gene transfection is unsettled and the underlying trafficking mechanism of exogenous genes in engineered single cells is not announced. Therefore, the engineered microarray biochips were conceptualized and prepared by the synthesized photointelligent biopolymer to precisely manage geometric topological structures (cell size and antenna-like protrusion) of stem cells on biochips. The cytoskeleton could be regulated in engineered cells and large cells with more antennas assembled well-organized actin filaments to affect cell tension distribution. The stiffness and adhesion force were measured by atomic force microscope to reveal cell nanomechanics on microarray biochips. Cytoskeleton-mediated nanomechanics could be adjusted by actin filaments. Gene transfection efficiency was enhanced with increasing cell nanomechanics, which was also confirmed by the evaluation of cell internalization capacity of nanoparticles and DNA synthesis ability. This work will provide a new strategy to study functional biomaterials, microarray chips and internal mechanism of gene transfection in patterned stem cells on biochips.Graphical abstract
研究领域:
生物医学工程
·
分子生物学
·
纳米技术
·
干细胞研究
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 22
·4882-4889
·
IF 7
Yu-xian Lai,Jia-yin Fu,Shao-fei Wu,Ren-yun Li,Jia-qi Hu,You-xiang Wang,M. Cristina L. Martins,Ke-feng Ren,Jian Ji,Guo-sheng Fu
Drug-coated balloon (DCB) is a therapeutic method that can effectively deliver antiproliferative drugs such as paclitaxel and rapamycin (RAPA) with no permanent implants left behind. However, delayed reendothelialization due to the toxicity of the delivered drugs leads to poor therapeutic effects. Here, we propose a new design of DCB coating, which incorporates both vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pDNA) that can promote endothelial repair and RAPA into protamine sulfate (PrS). We demonstrate that the PrS/pDNA/RAPA coating had stability and good anticoagulation properties in vitro. We further show that the coating exhibited excellent transfer capacity from balloon substrates to vessel walls both in vitro and in vivo. Furthermore, the PrS/pDNA/RAPA coating effectively inhibited neointimal hyperplasia after balloon-induced vascular injuries through the down-regulation of the mammalian target of Rapamycin (mTOR) and promoted endothelium regeneration through increased expression of VEGF in vivo. These data indicate that our nanocomposite coating has great potential for use as a novel coating of DCB to treat neointimal hyperplasia after vascular injuries.
研究领域:
心血管医学
·
药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2019
·Vol. 8
·期 8
·1800934
·
IF 6.27
Yuan Liu,Dan Chen,Jialin Li,Dengning Xia,Miaorong Yu,Jinsong Tao,Xinxin Zhang,Li Li,Yong Gan
Gene vectors for oral delivery encounter harsh conditions throughout the gastrointestinal tract, and the continuous peristaltic activity can quickly remove the vectors, leading to inefficient intestinal permeation. Therefore, vectors have demanding property requirements, such as stability under various pH and, more importantly, efficient uptake in different intestinal segments. In this study, a functional polymer, cholesterol-grafted poly(β-amino ester) (poly[hexamethylene diacrylate-β-(5-amino-1-pentanol)] (CH-PHP)), is synthesized and electrostatically interacted with plasmid DNA to form a CH-PHP/DNA complex (CPNC). This complex is designed to target the Niemann–Pick C1-like receptor, a cholesterol receptor, to improve oral gene delivery efficacy. With the presence of cholesterol, CH-PHP shows mitigated cytotoxicity, enhanced enzyme resistance, and improved gene condensing ability. CPNC further contributes to ≈43.1- and 2.3-fold increases in luciferase expression in Caco-2 cells compared with PNC and Lipo 2000/DNA complexes, respectively. In addition, the in vivo transfection efficacy of CPNC is ≈4.1-, 2.1-, and 1.6-fold higher than that of Lipo 2000/DNA complexes in rat duodenum, jejunum, and ileum, respectively. Therefore, CPNC may be a promising delivery vector for gene delivery, and using a cholesterol-specific endocytic pathway can be a novel approach to achieve efficient oral gene transfection.
研究领域:
药剂学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
MACROMOLECULAR BIOSCIENCE
·
2021
·Vol. 21
·期 6
·2100048
·
IF 4.979
Huiting Jia,Xindong Wang,Zhaoming Chen,Shuai Liu,Tongtong Zhou,Hao Zhou,Tianying Guo
Zinc ion complexes of dipicolylamine analogs, due to the strong synergistic effect between the Zn 2+ complex of containing polypyridine derivatives and polycations in each key step of pDNA transport, have been used as the third component to mediate polyethyleneimine with molecular weight 1.8 kDa (PEI1.8k)/DNA gene delivery system. And the effects of different structural characteristics, such as the number of pyridinamine ligands, the hydrophilic-hydrophobicity of the adjacent groups, on the in vitro transfection performance of the ternary complex are systematically investigated. This ternary hybrid system provides an effective strategy to improve the gene delivery of cationic polymers.
研究领域:
生物化学
·
分子生物学
·
基因治疗
✓ 已验证
DOI
高影响因子
RSC Advances
·
2014
·Vol. 5
·期 11
·8404-8414
·
IF 3.708
Yongbo Yang,Jinrui Wang,Xiaoda Li,Li Lin,Xiuli Yue
This paper reported the development of a multifunctional contrast agent for near infrared (NIR) fluorescent/ultrasonic bimodal imaging and gene delivery. CuInS2–ZnS alloyed quantum dots (ZCIS QDs) were coated with polyethyleneimine (PEI) to complex plasmid DNA (pDNA), followed by adsorption onto the surface of microbubbles (MBs) generated from the surfactant mixture of Span 60 and Tween 80. It was found that the obtained composite agent of MBs@QDs@PEI/pDNA had excellent capability to enhance both ultrasound and fluorescence imaging. In addition, an in vitro cell experiment showed that pDNA could be released from MBs@QDs@PEI/pDNA and internalized by target HeLa cells to realize a relatively high transfection efficiency by ultrasound-targeted microbubble destruction. Furthermore, the cytotoxicity, immune toxicity and histological evaluation showed that MBs@QDs@PEI/pDNA had a good biocompatibility for medical application. Therefore, such a multifunction agent could operate as a promising platform for targeting gene delivery under the guidance of NIR fluorescent/ultrasonic bimodal imaging.
研究领域:
医学影像
·
基因治疗
·
纳米技术
·
生物医学工程
✓ 已验证
DOI
高影响因子
Journal of Biomedical Nanotechnology
·
2016
·Vol. 12
·期 2
·261-273
·
IF 3.929
Qin Linghao,Cao Duanwen,Huang Huan,Ji Gangjian,Feng Min,Chen Jianhai,Pan Shirong
Polyamidoamine (PAMAM) dendrimers are a class of unique nanomaterials which attracted attention because of their extraordinary properties, such as highly branched structure and types of terminal primary groups. In addition, development in PAMAM chemical modification has broadened its
biological application especially for drug and gene delivery. In this study, PAMAMs are covalently conjugated onto α-Cyclodextrin (α-CD) via amide bonds obtaining the starburst cationic polymers (CD-PG2). The chemical structure and composition of CD-PG2 was characterized
by 1H NMR. Physicochemical and biological properties of CD-PG2/pDNA polyplex were evaluated by agarose gel retardation, stability test against DNase¢ñ, MTT assay, DLS measurement, CLSM observation, LDH leakage test, cellular uptake route analysis and in-vitro
cell transfection. Results showed that CD-PG2 can efficiently condense pDNA into nanoscale particles with a narrow size distribution, and protect pDNA form DNase I degradation. Compared with free PEI-25K and commercial product Lipofectamine2000, CD-PG2 shows excellent gene transfection efficiency
without serum interference as well as relatively low cytotoxicity. Cellular uptake of CD-PG2/pDNA polyplex is mainly through CME and CvME route and further investigations demonstrate that α-CD can regulate CvME pathway to improve polyplex transfection behavior. In conclusion,
CD-PG2 can be considered as a versatile tool for gene delivery, especially for gene transfer in-vivo.
研究领域:
纳米技术
·
分子生物学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2019
·
IF 4.784
Qing Liu,Zhu Jin,Wei Huang,Yuanyuan Sheng,Zhongmin Wang,Shengrong Guo
To overcome the different extra-/intracellular barriers in gene delivery, tumor-targeted and pH/redox-responsive ternary polyplexes with charge-conversional properties were prepared through a modular self-assembly strategy. Firstly, the thiolated trimethylated chitosan (TMC-SH) was synthesized to crosslink and condense pDNA through electrostatic interaction and disulfide formation, which obtained the TMC-SS/pDNA binary polyplexes with redox-responsive gene release. To further endow the binary polyplexes with tumor targeting and endo/lysosomal pH-triggered charge-reversal properties, a folate conjugated cis -aconitic amide-polyethylenimine (FA-PEI-AcO) was synthesized to shield the positive TMC-SS/pDNA, generating the FA-PEI-AcO/TMC-SS/pDNA ternary polyplexes with a size of ~190 nm and negative surface-charges. The ζ-potential of the polyplexes was stable at physiological pH and increased rapidly from -14 mV to + 20 mV at pH 5.5 (endo/lysosomal pH) due to the breakages of acid-liable amide bonds and the subsequent de-shielding of FA-PEI-AcO layers, which might benefit the endo/lysosomal escape of the polyplexes. Afterward, the polyplexes could redox-responsively release gene at higher intracellular concentrations of glutathione. By taking advantage of such multi-responses, significantly enhanced transfection efficiency was achieved in vitro in Hela cells for the ternary polyplexes. These results suggested that the newly developed polyplexes had potential application for gene delivery.
研究领域:
生物材料学
·
分子生物学
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
BIOCONJUGATE CHEMISTRY
·
2017
·
IF 4.818
Zhu Jiang,Qixian Chen,Xi Yang,Xiyi Chen,Zhen Li,De-E Liu,Wei Li,Yingjie Lei,Hui Gao
Tetraphenylene (TPE), characterized as a lipophilic and aggregation-induced-emissive fluorophore, was used to incorporate into an electrostatic self-assembled polyethylenimine-poly(ethylene glycol) (PEI–PEG)/plasmid DNA (pDNA) complexed micelle. The hydrophobic character of TPE appeared to drive a higher degree of condensation of the pDNA payload, which consequently resulted in not only strengthened colloidal stability of the constructed polyplex micelle but also improved biocompatibility by virtue of the elevated PEG crowdedness owing to the TPE-induced collapse of pDNA. These beneficial consequences potentially permitted a larger number of polyplex micelles to be internalized into the cells. PEG segments were designed to enable selective detachment from polyplex micelles in acidic milieu, e.g., the tumor microenvironment, and intracellular endosome compartment, based on the strategic arrangement of acid-responsive cleavable linkage between PEG and PEI. Upon PEG detachment, the exposure of cationic PEI/TPE polyplex was allowed to directly interact with the cell membrane, endosome membrane, and charged intracellular species, thus promoting cell internalization, endosome escape, and the release of the pDNA payload. Of note, this association of cationic PEI/TPE polyplex with the endosomal membrane could be further facilitated with the aid of lipophilic TPE, thereby eliciting pronounced destabilization potency to the endosome membrane and exerting an endosomal escape function. Eventually, the proposed system of these facile strategies, including responsive PEG detachment and functional TPE incorporation, was proven to provide efficient gene expression in the targeted tumors with an appreciable safety profile via systemic administration.
研究领域:
纳米医学
·
基因治疗
·
生物医学工程
·
材料科学
✓ 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）