Materials Science & Engineering C-Materials for Biological Applications
·
2017
·
IF 4.164
Jian-Tao Lin,Wen-Jia Pan,Jun-Ai Zhang,Wei Wang,Jia Zhong,Jia-Min Su,Tong Li,Ying Zou,Guan-Hai Wang
The codelivery of drug and gene is a promising method for cancer treatment. In our previous works, we prepared a cationic micelles based on chitosan and poly-( N -3-carbobenzyloxylysine) (CS-g-PZLL), but transfection ratio of CS-g-PZLL to Hela cell was low. Herein, to improve the transfection efficiency of CS-g-PZLL, curcumin was loaded in the CS-g-PZLL micelle. After irradiation, the obtained curcumin loaded micelle showed a better transfection, and the p53 protein expression in Hela cells was higher. The apoptosis assay showed that the complex could induce a more significant apoptosis to Hela cells than that of curcumin or p53 used alone, and the curcumin loaded micelle inducing apoptosis was best after irradiation. Therefore, CS-g-PZLL is a safe and effective carrier for the codelivery of drug/gene, and curcumin could be used as a photosensitizer to induce a photoenhanced gene transfection, which should be encouraged in improving transfection and tumor therapy.
研究领域:
生物医学工程
·
分子生物学
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT MOLECULAR MEDICINE
·
2018
·Vol. 18
·期 6
·383-391
·
IF 2.254
Li Yue,Lin Yan,Liufu Chun,Tu Jiawei,Yang Chaopin,Chen ZhiYi
Objective: To study transfection efficiency of folate-modified chitosan (FACS) nanoparticles as a non-viral vector delivering pEGFP-C3plasmid (FA-CS/P) to 293T cells with or without the combination of ultrasound and microbubble. Method: pEGFP-C3 was used as a reporter gene and
FA-CS nanoparticles, which were prepared by complex coagulation method, were used as biological carriers. Transfection efficiency to 293T cells mediated by FA-CS/P nanoparticles, ultrasound (US) and microbubble (MB) was assessed by fluorescence microscopy and flow cytometry. Result: FA-CS/P
nanoparticles have a particle size of 355.1 nm and zeta potential of 10.4 mV. Significant green fluorescence could be observed in CS/P group, FA-CS/P group, US+MB/P group, US+FA-CS/P group, Liposome 2000 (L) group under an inverted fluorescence microscope, while for US+MB+FA-CS/P group, only
scattered fluorescence was observed. Result of flow cytometry showed that the transfection rate of US+MB+FA-CS/P group was (2.0±0.2)%, which was significantly lower than other groups (P<0.05). CCK-8 experiments showed that cell vitality of US+MB+FA-CS/P was groups (P<0.05). CCK-8
experiments showed that cell vitality of US+MB+FA-CS/P was (64.1±4.6)%, which was also lower than other groups (P<0.05). Conclusion: In this study, FA-CS was successfully synthesized. FA-CS could combine with pEGFP-C3 effectively forming nanoparticles with nanoparticle size,
well dispersion, high encapsulation efficiency and no significant toxicity to cells. The application of ultrasound increased the transfection rate of FA-CS/P. However, while being exposed to ultrasound and microbubble, the transfection rate of FA-CS/P decreased obviously, may indicate that
there was no synergistic effect for gene transfection by the combination of ultrasound, folate modified chitosan and microbubbles.
研究领域:
生物医学工程
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 21
·2203252
·
IF 10
Xuan Nie,Wei You,Ze Zhang,Fan Gao,Xiao-Hong Zhou,Hai-Li Wang,Long-Hai Wang,Guang Chen,Chang-Hui Wang,Chun-Yan Hong,Qi Shao,Fei Wang,Lei Xia,Yang Li,Ye-Zi You
Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine-zinc (DPA-Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape.
研究领域:
生物医学工程
·
基因治疗
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2010
·
IF 7.365
Yilin Li,Xin Duan,Lihong Jing,Chunhui Yang,Ruirui Qiao,Mingyuan Gao
It was demonstrated that oligonucleotides , independent of their base sequence and length, could effectively induce the cellular uptake of mercapto acid-capped CdTe QDs after the oligonucleotides were covalently attached on the surface of the QDs. Following these experimental observations, a conjugate composed of covalently linked anti-survivin antisense oligonucleotides (ASON) and CdTe QDs was designed and synthesized. Then, the survivin mRNA down-regulation and the apoptosis of HeLa cells induced by ASON were studied. Systematic experimental results revealed that CdTe-ASON could effectively induce the apoptosis of HeLa cells, while CdTe QDs offered the possibility to visualize the specific intracellular localization of the CdTe-ASON probes strongly associated with their biological functions.
研究领域:
分子生物学
·
纳米医学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 3
·期 4
·642-650
·
IF 0
Jia Lv,Hong Chang,Yu Wang,Mingming Wang,Jianru Xiao,Qiang Zhang,Yiyun Cheng
Polyethylenimine (PEI) is one of the most promising polymeric gene vectors, however its applications are limited by serious cytotoxicity and moderate transfection efficacy. Fluorination is an efficient strategy to improve the transfection efficacy of cationic polymers while reducing their cytotoxicity. Here we grafted different fluoroalkyl chains to PEI via oxirane and anhydride reactions. The fluorinated PEIs show superior transfection efficacy on both 2D and 3D cell cultures to unmodified PEI. These fluorinated polymers allow efficient gene transfection at relatively low nitrogen to phosphorus ratios and thereby ensure low cytotoxicity on the transfected cells. Fluorinated PEIs prepared via the oxirane reaction are much more stable in aqueous solutions than the ones prepared by the anhydride reaction and show reproducible gene transfection during a period of 6 months. This study extends the applicable scope of fluorination on improving the transfection efficacy of polymers and generates a list of gene vectors for efficient 2D and 3D cell culture gene transfection.
研究领域:
生物材料学
·
基因治疗
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
Biomaterials Science
·
2014
·Vol. 3
·期 3
·500-508
·
IF 0
Naimin Shao,Hui Wang,Bingwei He,Yu Wang,Jianru Xiao,Yitong Wang,Qiang Zhang,Yujia Li,Yiyun Cheng
Dendrimers have shown great promise in the design of efficient gene vectors. However, high transfection efficacy is usually associated with serious cytotoxicity for these cationic polymers. Here, we report a facile strategy to prepare surface-engineered dendrimers with a dramatic transfection efficacy and reduced cytotoxicity. Surface-engineered dendrimers with multiple hydrogen bonding ligands such as guanamine and nucleobase derivatives show superior efficacy and low cytotoxicity on commonly used cells as well as 3D tumor spheroids to representative transfection reagents such as Lipofectamine 2000. Complementary multiple hydrogen bonding interactions between the modified ligands and DNA nucleobases play essential roles in efficient gene transfection. The hydrogen-bond modulation strategy represents a promising tool in the design of highly efficient and less cytotoxic gene materials.
研究领域:
生物化学
·
基因治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
Materials Today Bio
·
2025
·
IF 10.2
Ruirong Wu,Xiufeng Wu,Lan Zhang,Feng Zhang,Yang Ding,Yong Mao,Jiang Ni
Viral vectors share unparalleled gene-transfection efficiency due to protein capsid-mediated target-cell recognition and efficient cellular translocation, but clinical applications are seriously hampered by potential biosafety issues. Herein, we develop a virus-mimicking nanoparticle to enable safe, selective, and efficient TRAIL-expressing plasmid (pTRAIL) transfection for site-specific apoptosis and bystander effects. For preparation, a reactive oxygen species (ROS)-responsive phenylboronic acid-rich quaternized polymer (CRP) is synthesized for electrostatic compression of pTRAIL and coordinative coupling for apolipoprotein A-I with iRGD peptide conjugation, which is termed as iaCRP/pTRAIL nanoparticles with “gene core-protein shell” structure. The tailored virus-mimicking nanoparticles could prevent pTRAIL payloads from serum elimination, accompanied by site-specific accumulation and penetration. After cellular internalization, ROS-triggered nanoparticles disassembly could further perform burst pTRAIL release and high TRAIL expression. Our findings confirm TRAIL-derived apoptosis and bystander effects, giving in vivo tumor inhibition of ∼80 % and metastasis suppression of over 90 %. Collectively, the virus-mimicking strategy provides novel insights into bionic gene delivery and transfection design for efficient and safe oncotherapy.
研究领域:
生物医学工程
·
肿瘤学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2014
·
IF 8.312
Juan Zhang,Zhen Wang,Weifeng Lin,Shengfu Chen
Safety and high efficacy of vectors are essential requirements for gene therapy. To address these challenges, poly(carboxy betaine methacrylate ethyl ester)-poly(carboxy betaine methacrylate) (PCBMAEE-PCBMA) diblock copolymers were synthesized to form core–shell vector for gene delivery. The hydrophobic PCBMAEE segment, a polyzwitterionic precursor, can condense plasmid DNA (pDNA) into a hydrophobic core, which improves pDNA protection from nuclease attack and maintains the condensed structure against dilution. Moreover, the hydrolysis of PCBMAEE in uptaken gene vectors can enhance the pDNA release and reduce the cytotoxicity caused by the cationic polymer accumulation in the host cells. The PCBMA segment, zwitterionic fouling resistant material , is utilized to stabilize the gene vector in the complex medium and reduce the interference from serum proteins without impeding the endocytosis of DNA vector like PEG protection layer. Results showed that the complex formed by PCBMAEE 50 -PCBMA 14 with luciferase or pEGFP gene exhibit higher transfection efficacy of pDNA than that formed by PEI 25 kDa or Lipofectamine ® 2000 in tested cell lines (COS-7, HepG-2, HeLa, and HUVEC), especially, in difficult-to-transfect ones, such as HeLa and HUVEC. The luciferase expression level infected by the vectors of PCBMAEE 50 -PCBMA 14 /pGL-4 at N/ P = 20/1 is 27 times of the branched PEI 25 kDa in COS-7 cells and 16 times of Lipofectamine ® 2000 in HUVEC. Furthermore, the complex formed by PCBMAEE 50 -PCBMA 14 also show advantages in transfection rate, dosage effectiveness and preservation of transfecting activity in serum contained growth medium. The luciferase expression of the vectors of PCBMAEE 50 -PCBMA 14 /pGL-4 at N/ P = 20/1 is 230 times higher than that of PEI complex at low vector dosage (the 5% standard dosage). And the transfection rate is 25 times higher than that of PEI complex in 10% serum contained growth medium. In short, all these results indicated that the polymeric gene vector, consisted of convertible hydrophobic polyzwitterionic precursor and fixed polyzwitterionic fouling resistant segment, is a promising candidate for high and stable gene transfection in complex growth medium.
研究领域:
分子生物学
·
基因治疗
·
生物材料学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2018
·Vol. 42
·期 16
·13375-13381
·
IF 3.201
Haobo Han,Wenqi Chen,Jiebing Yang,Jiayuan Zhang,Quanshun Li,Yan Yang
The modification of 2-amino-6-chloropurine on polyamidoamine was performed to synthesize a derivative, AP-PAMAM, which was then employed as a carrier for p53 gene delivery to achieve anti-tumor efficacy. Using a human prostate tumor cell line PC-3 as a model, enhanced expression level of p53 gene could be detected by RT-PCR, qPCR and western blotting. Based on the successful p53 gene transfection, an obvious anti-proliferative effect could be obtained, which was identified to be associated with the simultaneous induction of cell apoptosis and cell cycle arrest at the G1 phase. The cell apoptosis was elucidated to be triggered by the activation of the mitochondria-dependent apoptotic signaling pathway. In addition, AP-PAMAM/p53 transfection could restrain the migration of tumor cells as demonstrated by wound healing and Transwell migration assays. Notably, AP-PAMAM-mediated p53 delivery exhibited a stronger inhibitory effect on both cell proliferation and migration than the PAMAM/p53 group. In summary, AP-PAMAM/p53 transfection provided a promising route to achieve the p53-based gene therapy.
研究领域:
分子生物学
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
AUSTRALIAN JOURNAL OF CHEMISTRY
·
2015
·Vol. 68
·期 10
·1535-1542
·
IF 1.558
Hao Yu,Shufeng Li,Liandong Feng,Yucheng Liu,Xiaoliang Qi,Wei Wei,Junjian Li,Wei Dong,Hao Yu,Shufeng Li,Liandong Feng,Yucheng Liu,Xiaoliang Qi,Wei Wei,Junjian Li,Wei Dong
Magnetic polyethyleneimine (PEI) complexes have demonstrated to be simple and efficient vectors for enhancing gene transfection. However, the high cytotoxicity of PEI restricts its further application in vivo. In this study, we synthesized several low cytotoxicity biodegradable cationic polymers derived from PEI (Mw 600) linked with diglycidyl tartrate (DT-PEI) or its analogues (diglycidyl succinate (DS-PEI) and diglycidyl malate (DM-PEI); D-PEIs for all 3 polymers). Moreover, a type of biocompatible magnetic nanoparticles (MNPs) with negative charges was prepared to assemble with D-PEIs/DNA complexes via electrostatic interactions. The magnetic ternary complexes have appropriate sizes of 120–150 nm and zeta potential values of ~20–25 mV. The transfection ability and cell viability of D-PEIs increased as the amount of hydroxyl groups increased in the repeat unit, which indicated that increasing the hydroxyl number in the backbone of D-PEIs can enhance gene expression and decrease cytotoxicity in A549 cells. Magnetofection of DT-PEI showed similar transfection efficiency with 30 min incubation; in contrast, the standard incubation time was 4 h. All three magnetic complexes displayed lower cytotoxicity when compared with those of PEI complexes in COS-7 and A549. These results indicated that these series of magnetic PEI derivatives complexes could be potential nanocarriers for gene delivery.
研究领域:
生物医学工程
·
分子生物学
·
材料科学
✓ 已验证
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2022
·
IF 5.395
Yuxi Gao,Jiayu Zhao,Zichao Huang,Hanqin Zhao,Zhaopei Guo,Sheng Ma,Xing Tang,Wantong Song,Xuesi Chen
OX40 (CD134, TNFRSF4) is a member of the tumor necrosis factor receptor superfamily that can be activated by its cognate ligand OX40L (CD252, TNFSF4) and functions as a pair of T cell costimulatory molecules. The interaction between OX40 and OX40L (OX40/OX40L) plays a critical role in regulating antitumor immunity, including promoting effector T cells expansion and survival, blocking natural regulatory T cells (Treg) activity, and antagonizing inducible Treg generation. However, current OX40 agonists including anti-OX40 monoclonal antibodies (aOX40) have serious side effects after systemic administration, which limits their clinical success and application. Herein, we propose a strategy to reprogram tumor cells into OX40L-expressing “artificial” antigen-presenting cells (APCs) by OX40L plasmid-loaded nanoparticles for boosting antitumor immunity in situ. A novel gene transfection carrier was prepared by a modular hierarchical assembly method, which could efficiently transfect various tumor cells and express OX40L proteins on their surface. These surface-decorated OX40L proteins were proved to stimulate T cell proliferation in vitro while stimulating strong antitumor immune responses in vivo. Importantly, this in situ reprogramming strategy did not induce any toxicity as observed in aOX40 treatment, thus providing a novel method for immune checkpoint stimulator application.
研究领域:
免疫学
·
肿瘤学
·
纳米技术
·
基因治疗
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Di Gao,Jinbiao Gao,Ming Xu,Zhong Cao,Luyao Zhou,Yingqin Li,Xiaoyan Xie,Qing Jiang,Wei Wang,Jie Liu
For successful gene therapy, it is imperative to accumulate therapeutic gene in tumor tissues followed by efficiently delivering gene into targeted cells. Ultrasound irradiation, as a noninvasive and cost-effective external stimulus, has been proved to be one of the most potential external-stimulating gene delivery strategies recently in further improving gene transfection. In this study, we developed tumor-targeting ultrasound-triggered phase-transition nanodroplets AHNP-PFP-TNDs comprising a perfluorinated poly(amino acid) C11F17–PAsp (DET) as a core for simultaneously loading perfluoropentane (PFP) and nucleic acids, and a polyanionic polymer PGA-g-PEG-AHNP as the shell for not only modifying the surface of nanodroplets but also introducing an anti-Her2/neu peptide (AHNP) aiming to targeted treatment of Her2-overexpressing breast cancer. The results showed the average diameter of AHNP-PFP-TNDs was below 400 nm, nearly spherical in shape. The modification of PGA-g-PEG-AHNP not only increased the serum stability of the nanodroplets but also improved the affinity between nanodroplets and Her2-overexpressing breast cells. Both intratumor and intravenous injection of AHNP-PFP-TNDs into nude mice bearing HGC-27 xenografts showed that the gene transfection efficiency and the ultrasound contrast effect were significantly enhanced after exposed to the ultrasound irradiation with optimized ultrasound parameters. Therefore, this targeting nanodroplets system could be served as a potential theranostic vector for tumor targeting ultrasound diagnosis and gene therapy.
研究领域:
医学影像学
·
肿瘤学
·
基因治疗
✓ 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）