Development and Characterization of Nano-Dinaciclib in Combination with Nano-Talazoparib for the Treatment of Breast Cancer
Mentor: Sri Sridhar, PhD (Northeastern University)
Dinaciclib is a cyclin-dependent kinase (CDK) inhibitor that is currently being studied for the treatment of various cancers, particularly breast, lung and skin cancer. Dinaciclib has been shown to sensitize tumors that are intrinsically resistant to PARP inhibitors, another molecular inhibitor, to these drugs for more durable responses. Currently, Dinaciclib is administered as an infusion leading to a number of side effects and therefore requiring substantial supportive care. These toxic side effects are amplified when Dinaciclib is administered in combination with other drugs, such as PARP inhibitors. Although, through documented clinical trials, it has proven to be an effective treatment, a nanoformulation of Dinaciclib aims to target the tumor specifically, through the enhanced permeability and retention effect. By encapsulating the drug in the proper combination of polymers Dinaciclib remains shielded in the bloodstream and can circulate for extended periods of time, finally accumulating in the tumor tissue. The delayed breakdown and disbursement of Dinaciclib allows for more potent and precise drug delivery. This project aims to develop a stable formulation of Nano-Dinaciclib to be used in conjunction with an already developed formulation of Nano-Talazoparib, a PARP inhibitor. These two nanoparticle formulations will be used as a targeted treatment to effectively treat breast cancer without the enhanced toxicity that the combination of free drugs would yield.
Photo ND12-48hr TEM+Measurement shows a similar set of nanoparticles of the same batch with a clear distinction in the display of measurements of the particles. These measurements were made in order to confirm the size of the particles and move forward with testing the created formulation. The collected measurements are shown at the same magnification of 20,000X Source: