Platelet Microvesicles as Targeted Anti-cancer Drug Delivery Tools

This project is at the merger of the fields of « Cancer research » & “Biomedical engineering » because we engineer a nanomedicine platform using micro/nano-size platelet-derived vesicles carriers as dedicated drug delivery system to cancer cells. Rationale: We develop here a pragmatic and highly translatable clinical-grade biomedical engineering technology allowing preparing and using drug loaded platelet-derived microvesicles (PMVs) as “Trojan Horse” targeted drug delivery system (TDDS) platform against cancer. The strong scientific rationale relies in the fact that PMVs possess (a) the platelet membrane-decorated machinery for targeting and interacting with tumor cells, (b) a nanosize (ca. 150-250 nm) favoring any enhanced permeability and retention (EPR) effect, and (c) a physiological lipid bilayer membrane facilitating the functional crossing of biological barriers, fusion with the targeted cells, and release of the drug. This is a highly translatable approach as platelet collection, ex vivo processing, and transfusion are routine clinical procedures worldwide, thus making this cellular source truly more feasible than mesenchymal stromal cells (that needs ex vivo propagation as a source of extracellular vesicles). The project is fully in line with the development of clinical-grade cell-derived microvesicles and extracellular vesicles as the new frontier in nanomedicine and cancer treatment, allowing to overcome limits and drawbacks of current therapies, namely high systemic toxicity, poor bio-distribution, and lack of targeting. Long-term goal: (A) To provide the scientific foundation to develop a translatable, scalable, user’s friendly, bioengineering method allowing to reproducibly and reliably generate and purify drug-loaded PMVs for cancer patients’ treatment based on a Trojan Horse strategy, and (B) to design a medical device for ex vivo processing and production of drug-loaded PMVs for patients’ treatment using autologous or allogenic single-donor platelets. Specific aims: Our methodological design is divided into four complementary and overlapping lines of investigation: Aim 1. To engineer a protocol for optimal loading of DOX within PMV nanocarriers Aim 2. To engineer and validate a scalable purification process of PMV-DOX Aim 3. To characterize PMV and PMV-DOX, demonstrate safety & unveil DOX release profile Aim 4: To evaluate the efficacy, toxicity, and targeting capacity of PMV-DOX in in vitro and in vivo cancer models To achieve these goals, we are deploying a complementary approach bringing expertise in therapeutic blood products, hematology, nanocarriers, and cancer therapy. We expect to unveil new findings in the use of PMVs as realistic therapeutic frontiers for translational applications.