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Targeted protein polymer nanomedicines carrying rapamycin
S.K. Roberts, P. Shi, W. Wang, S. Aluri, J.A. MacKay
Eunoia Biotech, US
Keywords: micelles, protein-polymer, nanomedicines, block copolymers
Summary:
Rapamycin (Rapa) is a potent anti-proliferative drug used in a variety of cancers. However, some drawbacks such as severe cytotoxicity, low bioavailability and rapid clearance limit wider usage of free Rapa. To overcome these limitations, we aim to develop a drug-specific protein polymer nanocarrier for Rapa delivery by genetically conjugating a cognate Rapa receptor – FK506 binding protein (FKBP) onto the micelles assembled by Elastin-like Polypeptide (ELP) block copolymers (FSI). The high-avidity binding enables a slow Rapa release from FSI with a half-life of 58h. Our studies have demonstrated the new Rapa formulation has greater efficacy and lower cytotoxicity than free Rapa in vivo. Furthermore, the approaches of genetic fusion of cognate drug receptor and co-assembly of micelles with different functional domains could be applied to more effectively deliver other drugs.
