The focus of our lab is the design and synthesis of monodisperse, targeted drug-delivery systems via polymer platforms.
The present-day challenge of delivering anti-cancer agents selectively to tumor cells to mitigate systemic toxicity has led to greater focus on drug delivery research using nanoscale carriers. Despite progress in pre-clinical studies, the therapeutic effects have not lived up to their expectations in the clinical setting. Though promising, these systems typically exploit passive delivery of a single therapeutic to the target tissue, for example, by the encapsulation of drugs in carrier systems followed by drug release under an external trigger. The current technologies suffer from issues of stability, large scale synthesis, distribution control, drug loading efficiency, and ease of transport across cell membranes. Our project will address this issue through the design and synthesis of the 2 components of a Smart Dual Acting Drug Delivery System (SDADDS) consisting of bifunctional nanocarriers capable of synergistic targeting of multiple drivers of cancer thereby overcoming current limitations to treating cancers. The dual components will consist of 1) extracellular receptor targeting through polyvalent binding to increase selective binding to cancerous cells and 2) Intracellular targeting by delivering chemotherapeutics selectively through controlled photo release. A designed bifunctional nanocarrier will have a targeting agent that binds to and inhibits a cell surface receptor highly overexpressed in tumor cells, coupled to a multiplexed anti-tumor drug that can be released locally by photolysis, affecting high spatiotemporal control for delivering the drug at high concentration.
The design and synthesis of the SDADDS dendrons will be customizable to a variety of tumor types with individualized combinations of high affinity receptor ligands and anti-cancer therapeutics. Triple Negative Breast Cancer (TNBC) is an ideal model system to test the effectiveness of a new SDADDS due to the challenges associated with treating this aggressive cancer which is poorly or unresponsive to traditional treatments under conditions seeking to minimize systemic toxicity. Completion of these studies will lead to an innovative platform that can provide dual targeting of specific types of tissues. The long-term objective is to customize the system to different cancer types creating personalized treatment to cancer patients particularly for late-stage detection disease states and drug resistant tumor types.
BS, Biochemistry (1998), PhD, Chemistry (2003)
ORCID iD is 0000-0001-6633-4976
MyNCBI link scdimaggio@orcid
Selected Publications:
1. Dougherty, C. A.,Furgal, J. C., van Dongen, M. A., Goodson, T., Banaszak Holl, M. M., Manono,J. and DiMaggio, S. Isolation and Characterization of Precise Dye/DendrimerRatios. Chem. Eur. J., 2014, 20(16), 4638-4645.
2. Generation 3 PAMAM Dendrimer TAMRA Conjugates Containing Precise Dye/Dendrimer Ratios Janet Manono, Casey A. Dougherty, Kirsten Jones, Joshua DeMuth, Mark M.Banaszak Holl and Stassi DiMaggio Materials Today Communication, 2015, 4.86-92.
3. SriramVaidyanathan, Milan Kaushik, Casey Dougherty, Rahul Rattan, Sascha N. Goonawardena,Mark M Banaszak Holl, Janet Monano, and Stassi DiMaggio. Increase inDye: Dendrimer Ratio Decreases Cellular Uptake of Neutral Dendrimers in RAWcells. ACS Biomater. Sci. Eng., 2016,2(9), 1540–1545.
Keywords: Targeted Drug-Delivery, Organic Synthesis, Polymer Functionalization
