Small molecule chemotherapeutics, although routinely used in the clinic, suffer from poor drug properties, including low water solubility, rapid plasma clearance, and non-specific bio-distribution causing toxic side effects. Our cognate drug receptor technology utilizes receptor-elastin like polypeptide (ELP) fusion proteins to facilitate delivery of drugs with sub-optimal physicochemical, toxicological, and pharmacokinetic properties.

For example, rapamycin, a clinically approved cytostatic and immunosuppressant is insoluble in water. Thus it requires non-aqueous solvents for delivery, displays sub-optimal pharmacokinetics in humans, partitions heavily into red blood cells, and causes severe stomatitis, hypercholesterolemia, and hypertriglyceridemia. To address these issues, we engineered FKBP-ELP fusion proteins to enable potent and safer delivery of rapamycin. FKBP, a cognate protein receptor of rapamycin solubilizes and stabilizes the drug. Since these fusion proteins are appropriately sized nanoparticles, they can also extend the plasma residence time by slowing renal filtration and promoting tumor accumulation, thereby reducing drug toxicity. Moreover, the delivery vehicle being proteinaceous in nature, is bio-degradable and bio-compatible.

Based on the promising efficacy of Rapamycin loaded FKBP-ELP fusion proteins, we have expanded our technology to facilitate delivery of other potent small molecules, which we are evaluating in models of cancer and autoimmune disorders.

Selected Publications

Berunda Polypeptides: Multi-Headed Fusion Proteins Promote Subcutaneous Administration of Rapamycin to Breast Cancer In Vivo
Jugal P. Dhandhukia, Zhe Li, Santosh Peddi, Shruti Kakan, Arjun Mehta, David Tyrpak, Jordan Despanie, J. Andrew MacKay
Theranostics 2017; 7(16):3856-3872.

Elastin-based protein polymer nanoparticles carrying drug at both corona and core suppress tumor growth in vivo
Pu Shi, Suhaas Aluri, Yi-An Lin, Mihir Shah, Maria Edman-Woolcott, Jugal Dhandhukia, Honggang Cui, J Andrew MacKay
J Control Release. 2013 Nov 10; 171(3): 330–338.

A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in suppressing autoimmune dacryoadenitis in a mouse model of Sjögren’s syndrome
Mihir Shah,* Maria C. Edman,* Srikanth R. Janga, Pu Shi, Jugal Dhandhukia, Siyu Liu, Stan G. Louie, Kathleen Rodgers, J. Andrew MacKay, and Sarah F. Hamm-Alvarez
J Control Release. 2013 Nov 10; 171(3): 269–279.