Elucidation of cellular uptake and intracellular trafficking of heparosan polysaccharide-based micelles in various cancer cells.

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ID: 26407
2019
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Abstract
Heparosan polysaccharide, known as a heparin precursor, can be used in drug delivery systems due to its good biocompatibility and anti-cancer effect. But few studies on the cellular uptake mechanism of heparosan polysaccharide-based nanocarrier have been investigated. Therefore, the intracellular trafficking and the uptake mechanism of heparosan-based micelles by different tumor cells were investigated in this study. Heparosan-cholesterol amphipathic conjugates (KC) were constructed and doxorubicin (DOX) was loaded to prepare DOX/KC micelles. Different cancer cells were selected to find out the influence on DOX/KC uptake. There was an obvious difference in cytotoxicity and cellular uptake of DOX/KC in various cancer cells. Interestingly, DOX/KC micelles exhibited the strongest cytotoxicity against MGC80-3 cells and displayed highly cellular uptake by B16 cells. The results of the uptake mechanism showed that the internalization of DOX/KC micelles into MGC80-3 cells and A549 cells was mainly through clathrin-mediated endocytosis and macropinocytosis, while micropinocytosis, clathrin-mediated endocytosis and clathrin/caveolae -independent multi-pathways all contributed to the uptake of micelles in B16 cells. Furthermore, after being internalized by MGC80-3 cells, DOX/KC could escape from the lysosome and simultaneously be transported into the nucleus and mitochondria resulting in the greatest cytotoxicity. These results indicate that heparosan-based drug delivery systems may have different uptake and subcellular distribution behavior in tumor cells, and they will achieve the maximum efficacy only in specific kind of cancers.
Reference Key
qiu2019elucidationinternational Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Qiu, Lipeng;Shan, Xiaotian;Long, Miaomiao;Ahmed, Kamel S;Zhao, Li;Mao, Jing;Zhang, Huijie;Sun, Changling;You, Chongzhao;Lv, Guozhong;Chen, Jinghua;
Journal International journal of biological macromolecules
Year 2019
DOI
S0141-8130(18)37176-9
URL
Keywords Keywords not found

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