Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 21
·3832-3841
·
IF 4.872
Guan-Hai Wang,Guo-Liang Huang,Yi Zhao,Xing-Xiang Pu,Tong Li,Jun-Jie Deng,Jian-Tao Lin
Stimuli-responsive nanocarriers for anticancer drug and gene co-delivery are a promising strategy in cancer therapy due to their combination of chemotherapy and gene therapy. In this work, we developed a facile and effective method to fabricate stimuli-responsive nanocarriers for anticancer drug and gene co-delivery based on complexes of polyethylenimine (PEI) with an adenosine triphosphate (ATP) responsive aptamer duplex (ARAD). No chemical reactions or complex modifications were used in the construction processes. In this system, Doxorubicin-loaded aptamer duplex and plasmid DNA (p53) can be bound by PEI by electronic interactions to form stable complexes which effectively protect the aptamer and p53 from DNase degradation. The intercalated Dox can be released on-demand by a structural change in the aptamer duplex in an ATP-rich environment. The morphology and average size of the nanocarriers were characterized by zeta potential and transmission electron microscopy (TEM). The nanocarriers exhibit lower cell toxicity in HeLa cell lines relative to PEI. RT-PCR and Western blot analysis confirmed that p53 could be effectively delivered and expressed in HeLa cells by PEI/ARAD/p53 complexes. Moreover, the apoptosis percentage of HeLa cells treated with PEI/ARAD/Dox/p53 complex increased to 40.8%, compared to 24.7% for PEI/ARAD/Dox complex and 11.5% for PEI/ARAD/p53, respectively. The result demonstrated that the combinatorial delivery of Dox and p53 by nanocarriers could induce synergistic actions and lead to effective cancer cell apoptosis.
研究领域:
癌症治疗
·
药物递送系统
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2018
·
IF 5.738
Cuiping Jiang,Zitong Qi,Hengbo Jia,Yilei Huang,Yunbo Wang,Wenli Zhang,Zimei Wu,Hu Yang,Jianping Liu
In this work, we report on an ATP-responsive low-molecular-weight polyethylenimine (LMW-PEI)-based supramolecular assembly. It formed via host–guest interaction between PEI (MW = 1.8 kDa)-α-cyclodextrin (α-CD) conjugates and PEI1.8k-phenylboronic acid (PBA) conjugates. The host–guest interaction between PEI1.8k-α-CD and PEI1.8k-PBA was confirmed by the 2D-NOESY chromatogram experiment and competition test. The ATP-responsive property of the supramolecular assembly was evaluated by a series of ATP-triggered degradation and siRNA release studies in terms of fluorescence resonance energy transfer, agarose gel electrophoresis assay, and the time course monitoring of the particle size and morphology. Confocal laser scanning microscopy confirmed the intracellular disassembly of the supramolecular polymer and the release of siRNA. The supramolecular assembly showed high buffering capability and was capable of protecting siRNA from RNase degradation. It had high cytocompatibility according to in vitro cytotoxicity and hemolysis assays. LMW-PEI-based supramolecular assembly facilitated cellular entry of siRNA via energy-dependent endocytosis. Moreover, the assembly/SR-A siRNA polyplexes at N/P ratio of 30 was most effective in knocking down SR-A mRNA and inhibiting uptake of modified LDL. Taken together, this work shows that ATP-responsive LMW-PEI-based supramolecular assembly is a promising gene vector and has potential application in treating atherosclerosis.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Yawei Wang,Hongbing Lin,Xuetao Zhao,Tong Ding,Yuqin Shen
Periodontitis is a chronic inflammatory disease characterized by alveolar bone loss , which affects the integrity of the tissue supporting the teeth. Previous studies have shown that reactive oxygen species (ROS) can promote the secretion of inflammatory factors and cause alveolar bone inflammatory reactions and bone resorption. Therefore, scavenging ROS is important for reducing the expression of inflammatory factors and improving the inflammatory environment of alveolar bone tissue. Superoxide dismutase (SOD) is one of the most effective antioxidant enzymes for eliminating ROS, which can protect cells from ROS toxicity and reduce the level of intracellular oxidative stress and inflammation. However, SOD molecules have shortcomings, such as short half-life and insufficient stability, which limit the application of SOD in inhibiting periodontal bone resorption. The use of carrier zeolitic imidazolate framework-90 (ZIF-90) with ATP-responsiveness and good biocompatibility can protect SOD molecules, improve SOD stability, and achieve intracellular SOD delivery. Therefore, we fixed SOD into ZIF-90 using the co-precipitation method to prepare ATP-responsive [email protected] and designed a study to investigate the ability of ATP-responsive [email protected] to reduce the inflammatory response of lipopolysaccharide (LPS)-stimulated human osteoblast MG-63. In our study, the ATP-responsive assembly efficiently suppressed the levels of ROS and pro-inflammatory cytokines, showing great potential to ameliorate the levels of oxidative stress, reduce inflammation, and increase osteoblast activity. This provides a novel idea for the application of SOD in alveolar bone resorption.
研究领域:
药学
·
生物材料
·
口腔科学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Cuiping Jiang,Yuan Wang,Peiyi Liang,Yao Chen,Ziming Zhuang,Lu Zhang,Yankui Yi,Li Liu,Qiang Liu
Specific delivery of NCEH1 plasmid is a promising approach to boost the cholesterol removal from lipid-laden macrophages for antiatherosclerosis. Polyethylenimine (PEI) is one of the most efficient gene carriers among nonviral vectors. However, the high transfection activity of PEI is always accompanied by profound cytotoxicity. To tackle the paradox between transfection efficiency and safety, we constructed a novel ATP-responsive multifunctional supramolecular polymer by cross-linking functionalized low-molecular-weight PEI via a boronic ester bond for NCEH1 plasmid delivery. The supramolecular polymer could condense NCEH1 plasmids to form stable nanosized polyplexes when the w/w ratios of the polymer and gene were higher than 2. ATP-triggered degradation of the polymer and pDNA release were characterized by a series of studies, including 1H NMR, 31P NMR, XPS, agarose gel electrophoresis, and ethidium bromide exclusion tests. In addition, the changes in particle size and morphology were observed in the presence of ATP. Interestingly, the supramolecular polymer showed broad spectrum antioxidant activities by measuring the elimination rates of different reactive oxygen species. In addition, the supramolecular polymer displayed a high buffering capability and good cytocompatibility as demonstrated by the results of the buffering capacity, a hemolysis assay, and a cytotoxicity test. Importantly, it was revealed that the supramolecular polymer/NCEH1 plasmid polyplex formulated at a w/w ratio of 20 was most effective in enhancing cholesterol removal from lipid-laden macrophages and reducing the accumulation of lipid droplets as evidenced by transfection study, cholesterol efflux assay, and oil red O staining studies. Collectively, the ATP-responsive multifunctional supramolecular polymer holds great potential for safe and efficient gene delivery for antiatherosclerosis.
研究领域:
生物技术
·
药学
·
分子生物学
·
心血管疾病
✓ 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）