Combinational drug nanodelivery system using biomimicry
Biomimetic drug delivery systems offer new opportunities to mimic biological particulates including cells, vesicles, and viruses for enhancing biocompatibility and promoting therapeutic efficacy. As a simple and effective biomimetic approach, delivery vehicles coated with cell membranes are currently being intensely pursued to achieve a variety of merits such as prolonging circulation time, alleviating immunogenicity, and achieving active targeting ability. Versatile biomimetic drug delivery systems with high specificity are expected to develop given the complexity of biological entities with different types of membranes integrated with distinct bioactive components.
Platelets are an indispensable component of the blood stream with the ability of targeting injury sites to impede clot formation and maintaining the integrity of blood circulation. Recently, the recognition of interaction between platelets and circulating tumor cells (CTCs) in blood has aroused considerable attention because of its crucial contribution to tumor metastasis. The aggregation of platelets surrounding CTCs helps CTCs survive in the blood stream and spread to new tissues.
Researchers at NC State University’s Biomedical Engineering Department have recently developed a platelet-membrane (PM)-coated core-shell nanovehicle for the combinational delivery of two anti-cancer drugs: the extracellularly-active protein TRAIL, and the intracellularly-functional small molecule doxorubicin. Enabled by the high affinity between platelets and CTCs, this drug delivery platform successfully delivered TRAIL to cancer cell death receptors and resulted in endocytosis. Acidity in the lyso-endosome degrades the PM-coating, resulting in delivery of the encapsulated doxorubicin to the nuclei of the cells. This resulted in synergetic cytotoxicity.
- Biomimicry utilizes existing affinity between platelets and circulating tumor cells to enhance endocytosis.
- Combinational delivery of TRAIL and doxorubicin enables synergetic cytotoxicity.
- This powerful platform could be adapted for metastasis diagnosis.
About the Inventor
Dr. Zhen Gu is an Assistant Professor in the joint Department of Biomedical Engineering at North Carolina State University and the University of North Carolina at Chapel Hill. His work also supports the Molecular Pharmaceutics Division at the UNC Eshelman School of Pharmacy and Department of Medicine. His research interests include nanomedicine applications for anti-cancer and anti-diabetes as well as novel drug delivery formulations. Previously, Dr. Gu was a postdoctoral research scientist working with Dr. Robert Langer at the Massachusetts Institutes of Technology.