Abstract

1. Development of Polymeric and Liposomal Nanohybrids as Potential Targeting Drug Delivery SystemsJeromy T. Bentley, RET Fellow 2010Naperville Central High SchoolRET Mentor: Dr. Seungpyo Hong, PhDNSF- RET Program Introduction Abstract This year, an estimated 569,490 Americans are expected to die of cancer, more than 1,500 people a day. An estimated 1,529,560 new cases of cancer will be diagnosed in the U.S. in 2010.1 Cancer is the second most common cause of death in the US, exceeded only by heart disease. In the US, cancer accounts for nearly 1 of every 4 deaths. Most of the currently available chemotherapy treatments frequently accompany severe side effects due to high toxicity to normal cells and tissues, thus targeting tumor cells and tissues is a worthwhile endeavor. Passive targeting utilizes the enhanced permeability and retention (EPR) effect that is defined by leaky vasculature around tumors, resulting in the accumulation of the nanoscale delivery system at the tumor site.2 In order to take advantage of the EPR effect, a nanoscale delivery system needs to be in the range of 50-200 nm. The objective of the study was to encapsulate functionalized polyethyleneimine (PEI) into polymeric nanoparticles or liposomes at a controlled size range less than 200 nm. Two types of novel nanohybrid systems have been prepared that encapsulate PEI-Rhodamine (PEI-RHO) conjugates, as outlined in the hypothesis below. Polycations (positively charged polymers) have demonstrated potential as nonviral drug delivery systems, however high toxicity has hindered their applications in vivo. This is most likely due to the cationic surface that induces uncontrolled, spontaneous interactions with cells.3 For this reason, control over the cellular interactions of a potential drug delivery system would be beneficial. Two nanohybrid systems (100-150 nm in diameter) that combine the polycations with protective outer layers consisting of biodegradable polymers or liposomes were synthesized. Polyethylenimine (PEI), a common polycation, was employed after conjugation with rhodamine (RHO). Encapsulation of the PEI-RHO conjugates into: i) polymers of polyethylene oxide-b-polylactide (PEO-PLA) or ii) PEGylated anionic liposomes, resulted in the production of two new nanohybrid systems. The results present a potential drug delivery system with enhanced control over its biological interactions and passive targeting potential through size control. Hypothesis Materials and Methods Results . Conclusion/Future Studies Teaching Module Plan Acknowledgements • Who: Naperville Central students and Dr. Hong’s Lab • What: Mini-Conferences covering Polymer and Chemistry and Nanoparticle synthesis • Where: University of Illinois-Chicago • When: Summer 2011 • Why: Exposure of cutting edge research inspires students to study science in the future • NSF Grant # EEC-0743068 • Dr. Andreas Linninger, RET Program Director • Dr. Seungpyo Hong, Faculty Research Mentor • Suhair Sunoqrot, Graduate Research Mentor • Undergraduate/ Graduate staff in Dr. Hong’s Lab • University of Illinois- Chicago • Based on particle size and surface charge characterization studies, both nanoparticles have successfully been synthesized. • Successful conjugation of various pharmaceuticals with PEI and subsequent encapsulation can be studied in the future. • Successful passive targeting of cancer cells can also be studied in the future through cellular uptake and invitro studies. • American Cancer Society. Cancer Facts & Figures 2010. Atlanta: American Cancer Society; 2010. • Peer et al., Nanocarriers as an emerging platform for cancer therapy. Nature Nanotech. 2007, 2, 751-60. • Verma, I. M.; Somia, N., Gene therapy - promises, problems and prospects. Nature 1997,389 (6648), 239-242.