RSC Medicinal Chemistry
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2024
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IF 4.1
Ji-Chao Guo,Shi-Hui Deng,Shu-Min Zhou,Xuan Zhou,Jiajia Du,Si-Han Zhou,Qi-Hua Zhao,Zhong-Yan Cai,Xiaoxia Ren,Ming-jin Xie
There is significant value in developing multifunctional drug delivery systems with high therapeutic efficiency for diagnosing and treating tumors. In this study, we synthesized the ATP-triggered and pH-sensitive material ZIF-90 using the liquid-phase diffusion method. This was done to load 10-hydroxycamptothecin (HCPT), and the FA-PEG-NH2 conjugate was synthesized through an amidation reaction. We further modified the HCPT@ZIF-90 nanocomposite by employing the Schiff base reaction to create the HCPT@ZIF-90-PEG-FA nanomaterial. Drug loading test results revealed a high HCPT drug loading of up to 22.3% by weight. In the drug release experiment, the cumulative drug release of HCPT@ZIF-90 nanomaterials in pH 5.4 and ATP solutions was the highest after 72 hours. The active targeted delivery of FA and the dual-responsive release of HCPT by ZIF-90 significantly enhanced the therapeutic effect of HCPT@ZIF-90-PEG-FA on human colon cancer cells (HCT116). In the cytotoxicity test, when 100 μg mL−1 of HCPT@ZIF-90-PEG-FA was incubated with cells, the cell survival rate was 16.61 ± 1.19%, significantly lower than that of the other experimental groups. This result indicates that HCPT@ZIF-90-PEG-FA exhibits excellent anti-tumor activity. Cell cycle experiments have shown that HCPT@ZIF-90-PEG-FA may inhibit the proliferation of cancer cells by blocking DNA synthesis and halting cell cycle progression. Cell uptake experiments showed that HCPT@ZIF-90-PEG-FA was mainly present in the cytoplasm of HCT1116 cells, indicating successful cellular entry of the drug to exert its therapeutic effect. In vivo experiments also demonstrated that HCPT@ZIF-90-PEG-FA nanomaterials can effectively eradicate HCT116 tumors. The utilization of the nano-drug carrier ZIF-90, along with the modification with PEG-FA, notably improved the therapeutic efficacy of HCPT. These results suggest that the system, with its active targeted delivery of FA and dual-responsive release of HCPT, could present a novel strategy for treating human colorectal cancer.
研究领域:
药学
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肿瘤学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2021
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IF 4.539
Chenxi Yu,Wenyu Zhu,Zhaozhan He,Jin Xu,Fengyan Fang,Ziang Gao,Wenli Ding,Yixiang Wang,Jing Wang,Junqiao Wang,Ao Huang,Aohua Cheng,Yanhui Wei,Shiyun Ai
Poly(lactic-co-glycolic acid) (PLGA) based microparticles have been widely applied in drug delivery system, but pristine PLGA particles suffers from low efficiency in release and non-targeted effect for drug delivery system. Inspired by cancer cells environment, we have fabricated an ATP-triggered delivery system based on porous PLGA microspheres covering drug-loaded ZIF-90. The system contains controlled doxorubicin releasing because ZIF-90 nanocrystals are easily collapsed under exposing to high-concentration ATP environment. In addition, [email protected] microparticles also perform low toxicity and 2.37 % hemolysis, and improved fluorescence intensity of doxorubicin by loading riboflavin sodium phosphate benefited from their partial Förster resonance energy transfer. This novel ATP-triggered drug delivery system based on porous PLGA particles could be widely utilized to design effective drug release biomaterials for gastric and lung cancer.
研究领域:
药剂学
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生物材料
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癌症研究
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药物传递系统
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产品关联
DOI
高影响因子
Advanced Therapeutics
·
2024
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IF 3.7
Wenjuan Yang,Lingling Tian,Ning Zhao,Lingyan Feng,Bingpu Zhou,Yongheng Zhu,Xinghua Gao,Yuan Zhang
Zeolitic imidazole frameworks (ZIFs), which combine the favorable characteristics of tunable porosity, controlled structure, and facile functionalization, are explored as a novel class of nanocarriers for biomedical applications. In this study, different ZIF materials are investigated, including ZIF-8, ZIF-67, ZIF-90, ZIF-92, and ZIF-108, with the same sodalite topology as the adenosine-5′-triphosphate (ATP)-triggered drug delivery systems. Results indicated that ZIF-90 and ZIF-108 displayed good biological compatibility and efficiently accumulated in the mitochondria through competitive coordination between the metal nodes of the ZIFs and ATP, suggesting efficient intracellular delivery. With further interactions between these metal ions and ATP, the encapsulated drugs are released from the ZIF nanoparticles, thereby achieving optimal anti-tumor activity. Through a systematic evaluation of the physicochemical properties of different ZIFs, it demonstrates that the surface charges of ZIFs have a significant impact on the cytotoxicity of cells, whereas the Lewis basicity of imidazole-based ligands plays an essential role in the competitive coordination between the metal ions and ATP. These findings provide a potential method for screening ZIFs based nanocarriers with minimal toxicity and explain the different delivery efficiencies of these materials with similar topologies.
研究领域:
纳米技术
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药学
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生物医学工程
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材料科学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）