"Jing Xu Won the Research Poster Competition in 2012 National Cancer Institute’s Nanotechnology Alliance Principal Investigators Meeting"
Jing Xu, a doctoral candidate in Department of Pharmaceutical Science with specialization in Pharmaceutics and Drug Delivery, is awarded as one of poster presentation winners in 2012 National Cancer Institute Nanotechnology Alliance Principal Investigators Meeting. Ms. Xu is working in the laboratory of Distinguished Professor and Chair Mansoor Amiji, and her doctoral thesis research project is titled "Multimodal Therapeutic Approach for Pancreatic Cancer: Delivery of Combination wt-p53 Gene and Gemcitabine in Epidermal Growth Factor Receptor-Targeted Gelatin Nanoparticles”.
Pancreatic cancer is one of the most lethal diseases in United States and throughout the world. Although gene therapy has tremendous promise, the major challenge has been in the development of safe and effective delivery system. The objective of her project is to develop novel gelatin-based engineered nanovectors systems (GENS) for safe and efficient gene delivery in the treatment of pancreatic cancer.
Gelatin is one of the most versatile natural biopolymer, widely used in food and medicines. The innovative strategy for gene delivery relies on physical encapsulation of DNA into gelatin nanoparticles (non-condensing system), which preserves the supercoiled structure of the plasmid and improves the transfection efficiency upon intracellular delivery. Further surface modification of Poly (ethylene glycol) PEG on GENS provide long-circulation times and are preferentially targeted to the tumor mass due to the hyper-permeability of the vasculature by the enhanced permeability and retention (EPR) effect. In order to target on this pancreatic cancer cell line, epidermal growth factor receptor (EGFR) specific peptide is conjugated on the particle surface for active targeting on Panc-1 cells, which have high EGFR expression levels. Based on the above rationale, they designed this EGFR targeting peptide-modified thiolated gelatin nanoparticles for gene and small molecule drug delivery, while PEG is served as a linker between the nanoparticle and peptide.
With this system, she has showed in preliminary studies that both control and EGFR targeted thiolated gelatin nanoparticles can efficiently encapsulate plasmid DNA and preserve plasmid structure, protect them during intracellular transport. This system successfully transfected Panc-1 cells with therapeutic plasmid, which encoded wild type p53 protein and triggered apoptosis in pancreatic cancer cells. To further enhance the efficiency of the treatment, she has included gemcitabine into the gelatin nanoparticle system. Cytotoxicity studies have also shown that EGFR-targeted nanoparticles significantly enhance the toxicity of gemcitabine. Combinational treatments in cells also showed better therapeutic effects compared to single treatment. In biodistribution study, pegylated nanoparticles enhanced the circulation time in blood and EGFR-targeted nanoparticles showed quick uptake and high accumulation in tumors.
Their studies have suggested that EGFR-targeted thiolated gelatin nanoparticles can serve as a safe and efficient DNA and drug delivery system as a treatment for pancreatic cancer. The ongoing efforts in this project will focus on the evaluation of the combination treatment with drug and gene therapy, in vivo anti-tumor activity using a subcutaneous and orthotopic Panc-1 tumor model in immune-compromised SCID Beige mouse.
In Jing’s research, they have represented successful way for development of novel nanomedicine as integration of biological therapy and nanotechnology. These results have supported that non-condensing gene and drug delivery strategy for targeted therapy will eventually lead more innovative and efficient treatment for many diseases.
This study is supported by the National Cancer Institute's Alliance in Nanotechnology for Cancer through the Center for Cancer Nanotechnology Excellence (CCNE) grant U54-CA151881.