CARBOHYDRATE POLYMERS
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2017
·
IF 4.811
Yao Tong,Tsogzolmaa Ganbold,Huricha Baigude
Cationic polymers are powerful carriers for intracellular delivery of therapeutic nucleic acids. However, the positively charged macromolecules have considerable cytotoxicity and often induce irreversible damages to the cells and tissues, which greatly negate the clinical application of such materials as drug delivery system. Herein, we report the synthesis of novel amphoteric polymers based on curdlan, and the evaluation of their cytotoxicity as well as the nucleic acid delivery efficiency. β-(1,3)-polyglucuronic acid, a TEMPO-oxidized derivative of curdlan, was chemically modified by conjugation of tetraethylenepentamine. The resulting amphoteric polymers, denoted tetraethylenepentamine-curdlan (TEPAC) polymers have the degree of substitution (DS) ranging from 25% to 48%. The result of MTT assay indicated that TEPAC polymers have negligible cytotoxicity on HeLa cells and A549 cells. The novel amphoteric polymers efficiently bound with plasmid DNA and delivered pcDNA-eGFP plasmid to 293T cells and induced expression of GFP 48 h after the transfection. Moreover, TEPAC polymers delivered siRNA to HeLa cells and HepG2 cells in high efficiency, and induced significant RNAi for the expression of an endogenous gene. Collectively, our data demonstrate that the novel curdlan-based amphoteric polymers are biocompatible and may provide a highly efficient system for the delivery of therapeutic nucleic acids.
研究领域:
生物材料学
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分子生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
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2021
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IF 0
Hui-Zhen Yang,Ji Zhang,Yu Guo,Lin Pu,Xiao-Qi Yu
Nonviral gene vectors with stimulus responsiveness and self-reporting properties have broad application prospects in gene therapy. Herein, we developed a nanosized reduction-responsive cationic liposomal vector formed from DNS(Zn), in which a naphthalimide–sulfonamide group was used as the glutathione (GSH)-responsive group to generate a blue fluorescence signal at 458 nm. Macrocyclic polyamine (cyclen) was used as a cationic headgroup to facilitate Zn(II) coordination, which may reduce the cytotoxicity and improve transfection efficiency. The Zn-free and nonresponsive analogues were used for comparison. Fluorescent assays revealed that the GSH response of DNS(Zn) could increase the blue fluorescence signal and improve the DNA release in cells. The title material also showed higher positive ζ-potential than its nonresponsive analogue, resulting in stronger DNA binding ability and better cellular uptake. These advantages made DNS(Zn) a good candidate for nonviral gene delivery, and the transfection efficiency in HeLa cells was distinctly higher than that of its analogue and the commercially available transfection reagent. Besides plasmid DNA, DNS(Zn) could also deliver small interfering RNA (siRNA) with good gene silencing efficiency, extending the application of the liposomes. These results suggest that DNS(Zn) can serve as a highly efficient nucleic acid delivery vector with reduction-responsive fluorescence self-reporting ability in tumor cells.
研究领域:
生物化学
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分子生物学
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基因治疗
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产品关联
DOI
PubMed
Journal of Materials Chemistry B
·
2017
·Vol. 5
·期 28
·5597-5607
·
IF 4.543
Gerile Gerile,Tsogzolmaa Ganbold,Yizheng Li,Huricha Baigude
Intracellular delivery of genetic material is a potentially powerful therapeutic approach for the treatment of genetic diseases. However, the scarcity of biocompatible delivery systems is a tremendous barrier for the application of nucleic acid therapy in the clinic. Herein, we successfully created biocompatible nucleic acid delivery systems based on cationic lipids consisting of alternatively linked ornithine residues in the head group (denoted DoGo lipids). Transfection of the pcDNA3-eGFP plasmid into cells using DoGo lipids resulted in significant transfection efficiency without showing any apparent cytotoxicity. Meanwhile, DoGo lipids efficiently delivered siRNA to cancer cell lines and induced profound RNAi activity at a siRNA concentration as low as 5 nM. DoGo lipid driven delivery of a siRNA against polo-like kinase 1 (Plk1) in cancer cells induced significant morphological changes in the cell and the nucleus due to cell cycle arrest and inhibition of cell proliferation, a phenotype resulting from the decreased Plk1 protein level. Our findings demonstrate that DoGo lipids have great potential in clinical application for gene based therapy.
研究领域:
分子生物学
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基因工程
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药物学
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产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Fangling Li,Dongdong Cao,Lixia Yao,Wenyi Gu,Zhiyong Liu,Dongmei Li,Lin Cui
Kaposi’s sarcoma-associated herpesvirus (KSHV) can infect a variety of cells and cause malignant tumors. At present, the use of microRNA (miRNA) for anti-KSHV is a promising treatment strategy, but the instability and non-specific uptake of miRNA still limit its use in the treatment of KSHV. In the present study, we constructed a nano-drug delivery system employing chemical grafting and electrostatic adsorption to solve the problems of easy degradation and low cell uptake of miRNA during direct administration. This nano-drug delivery system is to graft 4-carboxyphenylboric acid (PBA) and lauric acid (LA) onto polyethylenimine (PEI) through amidation reaction, and then prepare cationic copolymer nanocarriers (LA-PEI-PBA). The drug-carrying nanocomplex LA-PEI-PBA/miR-34a-5p was formed after further electrostatic adsorption of miR-34a-5p on the carrier and could protect miR-34a-5p from nuclease and serum degradation. Modification of the drug-carrying nanocomplex LA-PEI-PBA/miR-34a-5p by targeted molecule PBA showed effective uptake, increase in the level of miR-34a-5p, and inhibition of cell proliferation and migration in KSHV-infected cells. In addition, the drug-carrying nanocomplex could also significantly reduce the expression of KSHV lytic and latent genes, achieving the purpose of anti-KSHV treatment. In conclusion, these cationic copolymer nanocarriers with PBA targeting possess potential applications in nucleic acid delivery and anti-KSHV therapy.
研究领域:
药学
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分子生物学
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纳米技术
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病毒学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 7
·1350-1358
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IF 5.344
Jianming Mao,Jianwei Wang,Guping Tang,Paul K. Chu,Hongzhen Bai
Incorporating metal elements into polymers is a feasible means to fabricate new materials with multiple functionalities. In this work, a metal coordinated cationic polymer (MCCP) was developed. Ferric ions were incorporated into the polyethyleneimine-β-cyclodextrin (PC) polymer chain via coordination to produce a zipped-up polymer with a micro-ordered and macro-disordered topological structure. By varying the metal concentration, a tunable superstructure could be formed on the nano-templates via the “zipping” effect. In addition, the physicochemical properties of the assembly of MCCPs and nucleic acids were tailored by tuning the composition of the metal ions and polymers. The loading efficiency of Rhodamine-B by MCCPs was enhanced. The in vitro and in vivo results showed that the hybrid materials could be adjusted to deliver nucleic acids or small molecules with good performance and acquired the capacity of generating reactive oxygen species in tumor cells. Thus, the tunable and multifunctional MCCP system has great potential in nanomedicine and biomaterial science.
研究领域:
生物材料科学
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纳米医学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 10
·期 21
·6230-6243
·
IF 7.59
Yuanji Feng,Zhaopei Guo,Jie Chen,Sijia Zhang,Jiayan Wu,Huayu Tian,Xuesi Chen
To improve the efficiency of nucleic acid and protein delivery by cationic polymers, there is a trade-off between increasing the positive charge density of cationic polymers and decreasing cytotoxicity. In this work, a strategy to introduce multiple interactions between the cell membrane and a delivery system based on cationic polymers was proposed. A novel delivery system consisting of PEI1.8k and an enhancer (LA-RT) was fabricated. The introduction of LA-RT contributed to multiple interactions between the delivery system and the cell membrane including electrostatic interactions, hydrogen bonding, hydrophobic interaction, and dynamic sulfur exchange reactions, which enabled efficient intracellular delivery of nucleic acids and proteins. For nucleic acid delivery, plasmid DNA and mRNA were loaded to realize CRISPR/Cas 9 gene editing in vivo and protein expression in vivo, respectively. For protein delivery, the delivery system carrying OVA protein and CpG formed a nano-vaccine, which induced enhanced humoral and cellular immunity in vivo. In addition, the delivery system based on PEI1.8k revealed negligible cytotoxicity. This work provided a novel strategy to prepare efficient delivery systems based on cationic polymers via the introduction of a multifunctional enhancer.
研究领域:
药学
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分子生物学
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生物技术
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免疫学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
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IF 13.3
Tong Li,Dianwei Wang,Meng Meng,Xiaoya Guo,Lin Lin,Zhiyu Yang,Zhen Li,Longwei Xiang,Cong Liu,Jie Chen,Xuan Pang,Kai Hao,Huayu Tian,Xuesi Chen
Numerous studies have established the promise of combining phototherapy and gene therapy. However, there are persistent obstacles hindering the full optimization of this combined therapeutic approach, such as the maximum development of photosensitizers and the construction of high-performance gene carriers. The LEGO stacking characteristics of COFs have brought infinite imagination to the construction of delivery systems, allowing for the design of responsive nano castles based on different application scenarios. Here, we have constructed a novel cationic multifunctional nano COF nucleic acid delivery system based on photosensitizer and cationic monomers. The long-range ordered structure of COF effectively regulates the spatial distribution of photosensitizer, thereby preserving their phototherapy efficacy. Simultaneously, the inherent cationic porous nanostructure equips COF with exceptional capabilities for delivering nucleic acids. This integrated multifunctional nano delivery system significantly enhances the combined efficacy of phototherapy and gene therapy. The phototherapy capacity of COF enables precise tumor elimination in a spatiotemporal manner, inducing robust ICD and activating immune cells at the tumor site. Furthermore, loaded siPD-L1 significantly enhances immune cell recognition and killing of tumor cells, effectively shielding mice from re-invasion and tumor metastasis. The development of multifunctional nanomedicine based on COF provides new ideas for efficient tumor combination therapy.
研究领域:
纳米医学
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治疗学
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分子生物学
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癌症研究
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材料科学
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2021
·
IF 4.539
Jin Cheng,Shuang Wang,Qianhao Min,Jie Song,Ye Tian
Therapeutic nucleic acid delivery to solid tumors remains a challenge due to enzymatic degradation in cellular uptake and endosomal escape process as well as limited cell permeability. Herein, we reconstructed adoptive-macrophages by integrating functional DNA nanostructure-loaded nucleic acid drugs for tumor immunotherapy. The combination of functional small interfering RNAs (siRNAs) and CpG into DNA tetrahedron (DNA-tet) could induce the repolarization of M2 phenotype macrophages to antitumor M1 type, and releasing proinflammatory cytokines to kill tumor cells. The DNA tet-CpG/siRNA-loaded macrophages show excellent cellular uptake efficiency, parallel delivery capability and induce evident apoptosis and necrosis for tumor cells in vitro. In 4T1 xenograft tumor-bearing mice models, the adoptive macrophage with DNA tet-CpG/siRNA could effectively suppress the growth of subcutaneous tumors persistently and have low side effect for major organs. In summary, our proposed combination therapy of immunological macrophage and DNA-tet-CpG/siRNA will supply new ideas for solid tumor therapy.
研究领域:
癌症治疗
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纳米技术
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免疫治疗
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药物递送系统
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）