Academic Journal
Clinical-grade cryopreserved doxorubicin-loaded platelets: role of cancer cells and platelet extracellular vesicles activation loop
| العنوان: | Clinical-grade cryopreserved doxorubicin-loaded platelets: role of cancer cells and platelet extracellular vesicles activation loop |
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| المؤلفون: | Wu, Yu-Wen, Huang, Cheng-Chain, Changou, Chun Austin, Lu, Long-Sheng, Goubran, Hadi, Burnouf, Thierry |
| المساهمون: | Ministry of Science and Technology, Taiwan, Ministry of Education, National Health Research Institute, Taiwan |
| المصدر: | Journal of Biomedical Science ; volume 27, issue 1 ; ISSN 1423-0127 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2020 |
| الوصف: | Background Human platelets (PLT) and PLT-extracellular vesicles (PEV) released upon thrombin activation express receptors that interact with tumour cells and, thus, can serve as a delivery platform of anti-cancer agents. Drug-loaded nanoparticles coated with PLT membranes were demonstrated to have improved targeting efficiency to tumours, but remain impractical for clinical translation. PLT and PEV targeted drug delivery vehicles should facilitate clinical developments if clinical-grade procedures can be developed. Methods PLT from therapeutic-grade PLT concentrate (PC; N > 50) were loaded with doxorubicin (DOX) and stored at − 80 °C (DOX-loaded PLT) with 6% dimethyl sulfoxide (cryopreserved DOX-loaded PLT). Surface markers and function of cryopreserved DOX-loaded PLT was confirmed by Western blot and thromboelastography, respectively. The morphology of fresh and cryopreserved naïve and DOX-loaded PLT was observed by scanning electron microscopy. The content of tissue factor-expressing cancer-derived extracellular vesicles (TF-EV) present in conditioned medium (CM) of breast cancer cells cultures was measured. The drug release by fresh and cryopreserved DOX-loaded PLT triggered by various pH and CM was determined by high performance liquid chromatography. The thrombin activated PEV was analyzed by nanoparticle tracking analysis. The cellular uptake of DOX from PLT was observed by deconvolution microscopy. The cytotoxicities of DOX-loaded PLT, cryopreserved DOX-loaded PLT, DOX and liposomal DOX on breast, lung and colon cancer cells were analyzed by CCK-8 assay. Results 15~36 × 10 6 molecules of DOX could be loaded in each PLT within 3 to 9 days after collection. The characterization and bioreactivity of cryopreserved DOX-loaded PLT were preserved, as evidenced by (a) microscopic observations, (b) preservation of important PLT membrane markers CD41, CD61, protease activated receptor-1, (c) functional activity, (d) reactivity to TF-EV, and (e) efficient generation of PEV upon thrombin activation. The ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s12929-020-00633-2 |
| DOI: | 10.1186/s12929-020-00633-2.pdf |
| DOI: | 10.1186/s12929-020-00633-2/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s12929-020-00633-2 http://link.springer.com/content/pdf/10.1186/s12929-020-00633-2.pdf http://link.springer.com/article/10.1186/s12929-020-00633-2/fulltext.html |
| Rights: | http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.54A2D6C4 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12929-020-00633-2 |
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