Cationic Diblock Polymer-Drug Conjugate-Based Nanoparticles for Drug-Gene Co-Delivery

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Non-Technical: This award by the Biomaterials program in the Division of Materials Research to University at Buffalo, The State University at New York is to develop a novel drug-gene co-delivery system with potential applications in cancer treatment. Biodegradable polymers with two building blocks per molecule will be prepared. One building block will attach chemically anticancer drugs; the other building block will carry positive charges and can physically adsorb negatively-charged anticancer genes. The biodegradable polymers will assemble to form core-shell nanoparticles (NPs) in aqueous solutions, with inner core domains for drug loading and outer shell domains for gene loading. Comprehensive studies will be conducted to investigate the preparation and assembly of the biodegradable polymers, therapeutic delivery and degradation behavior of the assembled NPs, as well as the biomedical effects of the drug-gene co-delivery system on cancer cells and tissues. This project can lay a significant foundation for the further development of drug-gene combination therapies for the synergetic treatment of cancers. Outreach will be conducted through YouTube broadcasting of short polymer videos and educational activities directed to kids in local schools. Research participation of students from underrepresented groups will be guaranteed. Substantial efforts will also be made to update a classic polymer textbook.Technical: The goal of this project is to develop multifunctional biodegradable nanocarriers enabling not only noncompetitive high loadings of drugs and genes but also sustained release of these therapeutics. To this end, amphiphilic biodegradable di-block polymer-drug conjugates (PDCs) with a drug-conjugated block and a cationic block are designed as novel biomaterials for the preparation of multifunctional NPs, to integrate combination therapy, controlled release, imaging, targeting and biodegradability into one well-defined nanoscopic system for the precise delivery of both drug and gene. Well-defined di-block PDCs, as well as the corresponding assembled NPs with anticancer drug-conjugated cores and cationic shells, will be prepared and characterized. Drug conjugation, complexation with anticancer genes, drug/gene release profile, degradation behavior and multifunctionalization of the NPs will be studied. In vitro and in vivo studies using breast cancer models will be performed, and the anticancer efficacy of the multifunctional NPs with conjugated drug and complexed gene as compared to various controls will be evaluated. These NPs can serve as unique platforms for detailed systematic studies to understand and optimize the parameters governing the success of the co-delivery approach. The project will provide excellent interdisciplinary research opportunities for various students, including these from underrepresented groups. Broad educational outreach activities will be conducted.