Platelets and Platelet-Derived Microparticles for Trojan Horse Cancer Therapy (THCt)

Platelets and platelet microparticles (PMPs) can target specific cells (such as cancer cells) and can undergo endocytosis, thereby serving as an effective non-immunogenic, non-toxic, biodegradable cargo and good vehicle for drug delivery. In this research program, we evaluate the use of PMPs and platelets as drug carriers of encapsulated doxorubicin (DOX), with the ultimate strategy to develop therapeutic-grade autologous DOX-platelet and DOX-PMPs as “Trojan Horse” particles for cancer therapy. Our goal is (a) to provide a proof of concept that platelets, PMPs, and/or platelet-PMP combinations can be used to entrap and release anti-tumor agents and (b) to demonstrate, through in vitro and animal models, that this strategy may permit the administration of a much smaller, less toxic doses of chemotherapy to control tumor growth and metastasis. The conditions allowing suitable and reproducible entrapment of DOX in platelets (DOX-platelets) and PMPs (DOX-PMPs) will be determined. Impact of DOX entrapment on platelets activation and PMPs characteristics will be assessed by various biophysical and functional methods. This entrapment technology will be optimized, validated, and standardized using different platelet concentrates and PMP preparations to ensure reproducibility and define the quality requirements of the raw materials and of the processing methods. The capacity of DOX-platelets and DOX-PMPs to release DOX and induce cancer cell apoptosis will first be assessed in vitro using cancer cell lines (breast, ovary, lung, colon, prostate, and/or liver). Rodent cancer models will be used to assess the capacity of THCT using DOX-platelets and DOX-PMPs to effectively induce tumor regression. Free doxorubicin and liposomal doxorubicin will be used as controls to compare efficacy and toxicity. The fundamental objective of this pragmatic project is to prove the possibility to use GLP-grade DOX-platelets and DOX-PMPs as anticancer drug carriers for human clinical trials. Using PMPs-DOX can alleviate the side effects of chemoagents and enhance their anticancer effect. The results can serve to establish the basic knowledge needed for clinical trials using autologous platelet donations. Our research program encompasses nanomedicine, personalized medicine and cancer therapy. In the future, platelets and PMPs from patients’ own blood can serve as personalized non immunogenic autologous drug cancer delivery systems for cancer therapy and other diseases.