Hybrid Cancer Therapeutics

Andrew Pike

Deniz Cetin

Project: Hybrid Cancer Therapeutics

Lehigh University

Department of Chemical Engineering

Advisors: Professors Bryan W. Berger & Mark A. Snyder

Abstract:

In nano-scale drug delivery, when targeting cancer cells, a recurring challenge is that the more drug-resistant cancer cells survive the initial burst of drug and continue to metastasize into more resilient tumors. There are several size selective interfaces along the delivery pathway that the delivery system will be designed to permeate. For this reason, a delivery system with multiple phases of delivery is desirable. A solution to this is to control the rate of drug delivery through particle size, porosity, and architecture. In addition, pH responsive proteins can be used to target tumor sites and prevent drug release to healthy cell environments. Current approaches include organic particles tethered in order to target specific ligand, which create problems such as chemical instability, inefficiency in use of drug (reduced half-life in vivo), eliciting an immune response, and variable porosity. Our project focuses on tethering of mesoporous silica nanoparticles with peptides which change conformation when exposed to environments of different pH values and have certain protease-cleavage sites, with the purpose of creating an initial burst of cancer drug-carrier nanoparticles with sustained release.

Our approach seeks to minimize these problems by using particles of 5 nm in diameter to control the release of drug, while designing the peptide structure to react to changes in the tumor microenvironment. This ensures that the silica nanoparticles are not exposed to the environment and are not releasing drug until the delivery system reaches a tumor environment.