(120a) 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.