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Keywords {🔍}

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int/news-room/fact-sheets/detail/blood-safety eu/sites/default/files/medias/fichiers/good_practice_guidelines_dec_2013 buffy-coat-derived platelet concentrates circulatory-cell-mediated nanotherapeutic approaches plt-derived extracellular vesicles mouse anti-human cd41a-apc cancer cell-derived tf-evs plt-derived extracellular vesicle tissue factor–bearing microparticles tissue factor-rich microvesicles frac{\mathrm{amount}\ \mathrm{ tumor-shed vesicles depends van wordragen-vlaswinkel rj long-sheng lu drug-loaded plt-based therapy cell-mediated drug delivery plt-extracellular vesicles drug-resistant tumor growth chun austin changou article download pdf tumour cell-derived tf undergo long-term storage plt-cancer interaction loop grant number 104–2314-b-038-040-my3 mda-mb-231 cancer cells anticancer platelet-mimicking nanovehicles slow-release drug delivery optimizing circulation half-lives dual-layer surface coating anti-peg igm elicited plt-cancer intimate connection plt extracellular vesicle ev involving tf-ev delivering anti-cancer agents hydrophilic anti-cancer agents drug delivery strategies platelet membrane-functionalized particles adp-stimulated human platelets dmso-cryopreserved platelet concentrates horseradish peroxidase-conjugated antibodies mda-mb-231 cells/ml therapeutic-grade plt concentrate }\ \mathrm{plt}\ \mathrm{ ev expressing tf tissue factor-independent cryopreserved dox-loaded plt prepare dox-loaded plt mda-mb-231 cells incubated }\ \mathrm{dox}\ \mathrm{ tf-ev convert prothrombin

Payment Methods {📊}

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Questions {❓}

• PAS or plasma for storage of platelets?
• To exploit the tumor microenvironment: since the EPR effect fails in the clinic, what is the future of nanomedicine?

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WebPage:
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         headline:Clinical-grade cryopreserved doxorubicin-loaded platelets: role of cancer cells and platelet extracellular vesicles activation loop
         description: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. 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. 15~36 × 106 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 transfer of DOX from cryopreserved PLT to cancer cells was achieved within 90 min, and stimulated by TF-EV and low pH. The cryopreserved DOX-loaded PLT formulation was 7~23-times more toxic to three cancer cells than liposomal DOX. Cryopreserved DOX-loaded PLT can be prepared under clinically compliant conditions preserving the membrane functionality for anti-cancer therapy. These findings open perspectives for translational applications of PLT-based drug delivery systems.
         datePublished:2020-03-23T00:00:00Z
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            Cryopreserved platelet
            Tissue factor
            Cancer
            Doxorubicin
            Platelet extracellular vesicles
            Drug delivery
            Biomedicine
            general
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      headline:Clinical-grade cryopreserved doxorubicin-loaded platelets: role of cancer cells and platelet extracellular vesicles activation loop
      description: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. 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. 15~36 × 106 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 transfer of DOX from cryopreserved PLT to cancer cells was achieved within 90 min, and stimulated by TF-EV and low pH. The cryopreserved DOX-loaded PLT formulation was 7~23-times more toxic to three cancer cells than liposomal DOX. Cryopreserved DOX-loaded PLT can be prepared under clinically compliant conditions preserving the membrane functionality for anti-cancer therapy. These findings open perspectives for translational applications of PLT-based drug delivery systems.
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      dateModified:2020-03-23T00:00:00Z
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         Cryopreserved platelet
         Tissue factor
         Cancer
         Doxorubicin
         Platelet extracellular vesicles
         Drug delivery
         Biomedicine
         general
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      name:Graduate Institute of Translational Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
      name:Graduate Institute of Translational Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
      name:The Ph.D. Program for Cancer Biology and Drug Discovery, Center for Translational Medicine, Taipei Medical University, Taipei, Taiwan
      name:Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
      name:International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
      name:Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan
      name:Translational Laboratory, Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan
      name:International PhD Program in Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
      name:Saskatoon Cancer Centre and College of Medicine, University of Saskatchewan, Saskatchewan, Canada
      name:Graduate Institute of Biomedical Materials and Tissue Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
      name:International PhD Program in Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan
      name:International PhD Program in Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

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