LANGMUIR
·
2024
·
IF 3.7
Xiaoqiang Zhang,Jianmei Han,Ting Ding,Jianye Cao,Xingjie Zan,Yan Guo,Hongdan Bao
The intracellular fate of drug carriers had received extensive attention, which was profoundly influenced by the shapes of carriers. However, it has not been fully addressed due to the lack of effective strategies to prepare carriers with different shapes and the interference of other parameters (such as stiffness and chemistry of the shaped particle and the different cell lines). In this work, polymer-based microcapsules with different shapes (spherical, peanut, dumbbell, and cubic) but the same surface chemistry were engineered through the alternative deposition of polyethylenimine (PEI) and polyethylene glycol (PEG) onto the sacrificial CaCO3 templates with different well-defined shapes. Various techniques (SEM, CLSM, AFM, FTIR, and XPS) were utilized to determine the shapes and chemical composition of these microcapsules. The effect of microcapsule shape on cellular internalization kinetics and the endocytosis mechanism was thoroughly studied, and dumbbell and cubic microcapsules showed greater internalization rates and amounts than spherical and peanut microcapsules. These microcapsules were internalized through micropinocytosis, and the shapes had no obvious effect on the endocytosis mechanism. This work provides a wealth of information about the relationship between the shape of microcapsules and their performance in cellular internalization, which will be of great help in the development of related drug carriers.
研究领域:
药学
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生物材料
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细胞生物学
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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
CELL PROLIFERATION
·
2019
·Vol. 52
·期 3
·e12586
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IF 5.039
Yuanyuan Wei,Xiaoye Jin,Tingting Kong,Wenqing Zhang,Bofeng Zhu
Objectives This study aimed at investigating cellular uptake pathways of carbon dots (CDs) in human adenoid cystic carcinoma cell line ACC-2. Materials and methods We synthesized CDs using a hydrothermal method with citric acid and polyethylenimine (PEI, Mw = 25 000). The CDs incubated with the ACC-2 cells showed their bioimaging capabilities using a confocal microscopy test. Flow cytometry was used to analyse cellular uptake pathways of CDs in ACC-2 cells. Results Our findings indicated that CDs possessed good biocompatibility in ACC-2 cells. CDs were endocytosed mainly via micropinocytosis and energy-dependent pathways. Conclusions In general, these findings suggested that CDs had excellent biomedical imaging properties for ACC-2 cells and there was a potential opportunity to develop biomedical applications.
研究领域:
纳米技术
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生物医学工程
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癌症研究
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2020
·Vol. 8
·期 13
·3741-3750
·
IF 6.183
Song Zhang,Yiyun Cheng
Cytosolic protein delivery technique plays an important role in protein-based biotechnologies and therapeutics. However, the development of efficient nanocarriers for delivering cargo proteins into cytosols remains a continuing challenge due to the existence of multiple barriers. Here, we report an efficient strategy for the cytosolic delivery of native proteins by surface-engineered gold nanoparticles combined with hypertonicity treatment. Sub-10 nm gold nanoparticles stabilized by both cysteamine and 4-mercaptophenylboronic acid were used to complex cargo proteins via a combination of nitrogen-boronate coordination and ionic interactions. The yielding protein complexes with a size around 100 nm showed efficient endocytosis via micropinocytosis- and lipid raft-mediated pathways. Further the hypertonicity treatment of the transduced cells by glycerol, glucose, sucrose, and NaCl solutions efficiently facilitates the endosomal escape and the intracellular release of cargo proteins. By the proposed strategy, cargo proteins including bovine serum albumin, ovalbumin, green fluorescent protein, R-phycoerythrin, and horseradish peroxidase were successfully delivered into cell cytosol with maintained protein bioactivity. This study provides a feasible and efficient strategy for the intracellular protein delivery.
研究领域:
纳米技术
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生物技术
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治疗学
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蛋白质工程
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2016
·
IF 8.854
Jinxie Zhang,Xudong Zhang,Gan Liu,Danfeng Chang,Xin Liang,Xianbing Zhu,Wei Tao,Lin Mei
The inner membrane vesicle system is a complex transport system that includes endocytosis, exocytosis and autophagy. However, the details of the intracellular trafficking pathway of nanoparticles in cells have been poorly investigated. Here, we investigate in detail the intracellular trafficking pathway of protein nanocapsules using more than 30 Rab proteins as markers of multiple trafficking vesicles in endocytosis, exocytosis and autophagy. We observed that FITC-labeled protein nanoparticles were internalized by the cells mainly through Arf6-dependent endocytosis and Rab34-mediated micropinocytosis. In addition to this classic pathway: early endosome (EEs)/late endosome (LEs) to lysosome, we identified two novel transport pathways: micropinocytosis (Rab34 positive)-LEs (Rab7 positive)-lysosome pathway and EEs-liposome (Rab18 positive)-lysosome pathway. Moreover, the cells use slow endocytosis recycling pathway (Rab11 and Rab35 positive vesicles) and GLUT4 exocytosis vesicles (Rab8 and Rab10 positive) transport the protein nanocapsules out of the cells. In addition, protein nanoparticles are observed in autophagosomes, which receive protein nanocapsules through multiple endocytosis vesicles. Using autophagy inhibitor to block these transport pathways could prevent the degradation of nanoparticles through lysosomes. Using Rab proteins as vesicle markers to investigation the detail intracellular trafficking of the protein nanocapsules, will provide new targets to interfere the cellular behaver of the nanoparticles, and improve the therapeutic effect of nanomedicine.
研究领域:
细胞生物学
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纳米技术
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药学
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2019
·Vol. 9
·期 1
·1-10
·
IF 4.011
Sun Xiangyu,Cheng Cheng,Zhang Jinxie,Jin Xing,Sun Shuqing,Mei Lin,Huang Laiqiang
3-hydroxybutyrate-co-3-hydroxyhexanoate (PHBHHx), which is naturally generated by biodegradable polyhydroxyalkanoates synthesized by bacteria, is an attractive material for drug delivery due to its controllable physical properties, non-toxicity, environmental friendliness, degradable properties and good biocompatibility. However, the intracellular trafficking network pathways, especially the autophagy mechanism of PHBHHx nanoparticles (NPs), have rarely been investigated. In this paper, we successfully prepared the NPs used solvent displacement method and investigated the autophagy pathways and other intracellular trafficking mechanisms based on NPs with the assistance of Rab proteins. We found that NPs were internalized in cells mainly via clathrin endocytosis and caveolin endocytosis. Beside the classical pathways, we discovered two new pathways: the micropinocytosis early endosome (EEs)-micropinocytosis-lysosome pathway and the EEs-liposome-lysosome pathway. NPs were delivered to cells through endocytosis recycling vesicles and GLUT4 exocytosis vesicles. Similar to other nanoparticles, NPs also induced intracellular autophagy and were then degraded via endolysosomal pathways. 3-MA and CQ were used as autophagy inhibitors to avoid the degradation of NPs through lysosomes by blocking endolysosomal pathways. Tumor volumes and weights were significantly decreased when autophagy inhibitors and chemical drugs packaged in NPs were cooperatively used.
研究领域:
纳米技术
·
药理学
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细胞生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Yajun Liu,Rui Dai,Qiuyu Wei,Wenzhe Li,Guang Zhu,Hao Chi,Zhaoming Guo,Li Wang,Changhao Cui,Jianqiang Xu,Kun Ma
Janus nanoparticles with an anisotropic feature concentrated multiple properties on a single carrier, providing synergistic effects. In this study, dual-functionalized Janus nanoparticles (HA-JMSN/DOX-DMMA) were constructed with a tumor-targeting ligand (hyaluronic acid, HA) modified on the one side and a charge reversal group (2,3-dimethylmaleic anhydride, DMMA) on the other side. The drug release of HA-JMSN/DOX-DMMA was positively correlated with the acidity of the environment. The cytotoxicity and cell uptake of HA-JMSN/DOX-DMMA were superior to the isotropous nanoparticles. The endocytosis pathway of HA-JMSN/DOX-DMMA involved the clathrin-mediated endocytosis (HA) and the micropinocytosis (DMMA) at the same time, which indicated that they both participated in the interaction between nanoparticles and tumor cells. After being injected intravenously in mice, the distribution of HA-JMSN/DOX-DMMA in tumor was enhanced significantly. The antitumor therapy study in vivo showed that HA-JMSN/DOX-DMMA inhibited tumor growth and improved the survival rate of tumor-bearing mice effectively. In general, HA-JMSN/DOX-DMMA could take the synergistic effect of active targeting and charge reversal to deliver drug in tumor cells and kill them efficiently, which was a promising antitumor nanodrug.
研究领域:
纳米技术
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药学
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癌症研究
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生物医学工程
✓ 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）