Remote-Loaded Platelet Vesicles for Disease-Targeted Delivery of Therapeutics.

The recent emergence of biomimetic nanotechnology has facilitated the development of next-generation nanodelivery systems capable of enhanced biointerfacing. In particular, the direct use of natural cell membranes can enable multivalent targeting functionalities. Herein, we report on the remote loading of small molecule therapeutics into cholesterol-enriched platelet membrane-derived vesicles for disease-targeted delivery. Using this approach, high loading yields for two model drugs, doxorubicin and vancomycin, are achieved. Leveraging the surface markers found on platelet membranes, the resultant nanoformulations demonstrate natural affinity towards both breast cancer cells and methicillin-resistant Staphylococcus aureus. In vivo, this translates to improved disease targeting, increasing the potency of the encapsulated drug payloads compared with free drugs and the corresponding non-targeted nanoformulations. Overall, this work demonstrates that the remote loading of drugs into functional platelet membrane-derived vesicles is a facile means of fabricating targeted nanoformulations, an approach that can be easily generalized to other cell types in the future.