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• W2316157369 abstract "// Lu Dai 1 , Ning Gu 2 , Bao-An Chen 1 and Gerard Marriott 2,3 1 Department of Hematology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China 2 School of Biological Science and Medical Engineering, Southeast University, Nanjing, China 3 Department of Bioengineering, University of California, Berkeley, CA, United States of America Correspondence to: Bao-An Chen, email: // Gerard Marriott, email: // Keywords : human platelets, repurposing platelets, tumor-targeting, in vivo imaging, myeloma xenotransplants Received : February 19, 2016 Accepted : March 28, 2016 Published : March 31, 2016 Abstract Human platelets were identified in tumors by Trousseau in 1865, although their roles in tumor microenvironments have only recently attracted the attention of cancer researchers. In this study we exploit and enhance platelet interactions in tumor microenvironments by introducing tumor-targeting and imaging functions. The first step in repurposing human platelets as vehicles for tumor-targeting was to inhibit platelet-aggregation by cytoplasmic-loading of kabiramide (KabC), a potent inhibitor of actin polymerization and membrane protrusion. KabC-Platelets can accumulate high levels of other membrane-permeable cytoxins and probes, including epidoxorubicin, carboxyfluorescein di-ester and chlorin-e6. Finally, mild reaction conditions were developed to couple tumor-targeting proteins and antibodies to KabC-platelets. Fluorescence microscopy studies showed KabC-platelets, surface-coupled with transferrin and Cy5, bind specifically to RPMI8226 and K562 cells, both of which over-express the transferrin receptor. Repurposed platelets circulate for upto 9-days a feature that increases their chance of interacting with target cells. KabC-platelets, surface-coupled with transferrin and Cy7, or chlorin-e6, and injected in immuno-compromised mice were shown to accumulate specifically in sub-cutaneous and intra-cranial myeloma xenotransplants. The high-contrast, in vivo fluorescence images recorded from repurposed platelets within early-stage myeloma is a consequence in part of their large size (φ~2µm), which allows them to transport 100 to 1000-times more targeting-protein and probe molecules respectively. Human platelets can be configured with a plurality of therapeutic and targeting antibodies to help stage tumor environments for an immunotherapy, or with combinations of therapeutic antibodies and therapeutic agents to target and treat cardiovascular and neurologic diseases." @default.
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• W2316157369 date "2016-03-31" @default.
• W2316157369 modified "2023-09-24" @default.
• W2316157369 title "Human platelets repurposed as vehicles for<i>in vivo</i>imaging of myeloma xenotransplants" @default.
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• W2316157369 doi "https://doi.org/10.18632/oncotarget.8517" @default.
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