JOURNAL OF APPLIED POLYMER SCIENCE
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2024
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IF 2.7
Zhaoxia Liu,Lili Zhao,Wangwang Tao,Rui Chen,Yu Zhou,Hongxiang Chen,Hongye Yan,Xinghua Liao
In order to obtain a kind of anticancer drug delivery carriers with good stability in blood circulation, high cellular uptake, and controlled drug release ability, folate-modified polyurethane with disulfide bonds and amino groups (FPUSN) and polyurethane with carboxyl groups (PUC) were respectively synthesized. FPUSN and PUC could co-assemble in water to form nanomicelles (FPUSN/PUC) via electrostatic interaction. When the mass ratio of FPUSN to PUC was 12, FPUSN/PUC-12 micelles had obvious negative-to-positive charge-reversal property with decreasing pH from 7.4 to 5.0. Doxorubicin-loaded micelles (FPUSN/PUC-12@DOX) with negative charges showed excellent stability under simulated normal physiological condition. However, the charge-reversal happened at pH 6.5 and positive charges increased with the pH decrease. When the glutathione concentration was 10 mM, the structure of FPUSN/PUC-12@DOX micelles was broken. So FPUSN/PUC-12@DOX micelles exhibited significant acid/reduction-sensitive drug release properties and then DOX could be rapidly released in simulated tumor intracellular environment. Cellular experimental results demonstrated that FPUSN/PUC-12 micelles could enhance cellular uptake under acid condition and FPUSN/PUC-12@DOX micelles had better anti-proliferation effect against HGC-27 cells at pH 6.5 than that at pH 7.4 owing to multi-responsive synergistic effects. Therefore, FPUSN/PUC micelles will have great application potential as drug delivery carriers for enhancing anticancer efficacy.
研究领域:
生物材料学
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药剂学
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肿瘤学
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产品关联
DOI
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
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2015
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IF 3.088
Luyan Wu,Liping Zhang,Gang Shi,Caihua Ni
Zwitterionic nanoparticles have excellent serum stability. In this study, pH/redox responsive polymer was synthesized through a modification of dextran using succinic acid, followed by crosslinking with cystamine. The polymer could self-assemble into stable nanoparticles (NPs) in aqueous solution. The NPs carried certain amount of free carboxyl and amino groups on the surface, which endowed the NPs excellent anti-protein adsorption ability. The surface charge was negative at pH 7.4 and was converted to positive at pH 5.0. It was revealed that the NPs showed little non-specific protein adsorption and had excellent serum stability, and the NPs could be internalized in Hela cells rapidly. This result was ascribed to the charge reversible feature of the NPs. Doxorubicin (DOX) was loaded in the NPs for release studies in vitro. The DOX-loaded NPs exhibited obvious pH and reduction sensitivities in response to the environment in tumor cells due to the introduction of carboxyl groups, amino groups and disulfide bonds in the NPs. The NPs were biocompatible, biodegradable, and could be potentially applied as anticancer drug carriers for enhancement of tumor intercellular uptake of doxorubicin.
研究领域:
药剂学
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生物材料
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2023
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IF 5.1
Xueyan Hou,Yalin Guan,Sisi He,Zeqing Wu,Jintao Bai,Jingjing Xu,Jingwen Wang,Suyue Xu,Huiqing Zhu,Yanyan Yin,Xue Yang,Yongli Shi
Poloxamer 188 is a widely used pharmaceutical excipient, which can be found in a variety of drug formulations. In this study, a novel self-assembled nanoplatform was developed for active targeting of folate receptor-overexpressing triple-negative breast cancer. This platform, FPP NPs, was prepared by the retrofitted poloxamer 188 derivatives, resulting in nanoparticles with an appropriate size (< 100 nm), good stability, and satisfactory biocompatibility. Cellular uptake and in vivo distribution studies showed that the FPP NPs had strong tumor cell uptake and active targeting capabilities. Furthermore, docetaxel (DTX) was loaded into FPP NPs in this research. The resulting DTX/FPP NPs exhibited high drug encapsulation efficiency and drug loading capacity, and could rapidly release DTX under slightly acidic conditions, significantly increasing the antitumor activity of the encapsulated drug both in vitro and in vivo. In addition, DTX/FPP NPs could significantly decrease the hepatotoxicity and nephrotoxicity of DTX. Therefore, this drug delivery nanoplatform, based on retrofitted poloxamer 188 with self-assembly properties in aqueous solution and active targeting capabilities to tumors, may provide a promising approach for targeted treatment of triple-negative breast cancer.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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DOI
PubMed
高影响因子
Drug Delivery and Translational Research
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2023
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IF 5.4
Wang Yanzhi,Wang Linchao,Chang Hanyue,Shen Qing,Zhang Sai,Sun Shanshan,Liu Ying,Zheng Jiaxin,Liu Hongmin
In this study, we synthesized a novel compound, agmatine-cholesterol conjugate (AG-Chol), to enhance the anti-tumor activity of drug-loaded liposomes. We replaced cholesterol with AG-Chol in preparing doxorubicin hydrochloride (DOX) liposomes by using an active loading method for DOX. We assessed the physical and chemical properties of the resulting AG-Liposomes and evaluated their efficacy in vitro and in vivo. The results showed that AG-Liposomes were stable with high encapsulation efficiency. Compared with the control liposomes, AG-Liposomes exhibited a slower drug release rate in the release medium at pH 6.8. The in vitro cell experiments demonstrated that AG-Liposomes had higher tumor cell uptake rate, stronger migration inhibition rate, higher apoptosis rate, better anti-clonogenic ability, and higher lysosome escape ability than the control liposomes. In vivo distribution results demonstrate that liposomes prepared with AG-Chol instead of cholesterol can significantly enhance their tumor targeting abilities and reduce their distribution to non-targeted sites. In vivo tumor suppression experiments showed that AG-Liposomes had a higher tumor suppression rate than the control liposomes without causing apparent toxicity to normal tissues, as evidenced by histological staining. Therefore, substituting cholesterol with AG-Chol in the preparation of liposomes can result in enhanced lysosome escape, improved tumor targeting, and increased efficacy of anti-tumor drugs. Graphical Abstract
研究领域:
药学
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肿瘤学
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药物递送系统
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生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
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2024
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IF 4.5
Meiqi Xu,Junwei Liu,Jianming Yu,Jingwen Wang,Hui Li,Ting Zhong,Yanli Hao,Zhuoyue Li,Jingru Wang,Xu Huang,Hui Wang,Yubo Tian,Heng Zhao,Qingchao Wei,Xuan Zhang
Improving nanomedicine uptake by tumor cells is key to achieving intracellular drug delivery. In this study, we found that methyl-β-cyclodextrin (MβCD) can significantly promote the intracellular accumulation of nanoparticulated α-linolenic acid-paclitaxel conjugates (ALA-PTX NPs) via enhanced clathrin-mediated endocytosis and limited degradation in lysosomes. Our in vitro results indicated that MβCD not only reduced the plasma membrane cholesterol content and increased plasma membrane fluidity, leading to ALA-PTX NPs being more easily incorporated into the plasma membrane, further enhancing membrane fluidity and making the plasma membrane more susceptible to tensile deformation, forming intracellular vesicles to enhance ALA-PTX NP cellular uptake, but also destroyed lysosomes and then limited ALA-PTX NPs’ degradation in lysosomes. In HepG2 tumor-bearing mice, MβCD was also able to enhance the antitumor activity of ALA-PTX NPs in vivo. Moreover, we found that MβCD specifically promoted PUFA-paclitaxel conjugate NP cellular uptake. The cellular uptake of PTX liposome which shares an endocytosis pathway with ALA-PTX NPs could be enhanced by MβCD combined with ALA or ALA-PTX NPs. Therefore, we suggested that MβCD combined with polyunsaturated fatty acid-conjugation would be an effective strategy for improving intracellular delivery of nanoparticulated chemotherapeutic drugs used for combination administration to enhance antitumor efficiency.
研究领域:
药理学
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纳米技术
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肿瘤学
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细胞生物学
✓ 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）