The objective of this proposal is to develop approaches to enhance the delivery of nucleic acid based therapeutics to intracellular targets in Non-Hodgkin Lymphoma (NHL) cells. The project will utilize novel pH-sensitive """"""""smart polymer"""""""" based carriers to penetrate the endosomal barrier that limits entry to the cytoplasmic and nuclear compartments where antisense-ODN and siRNA exert their gene silencing effects. We believe that siRNA and AS-ODN have great potential for the treatment of NHL and hypothesize that improvement in delivery methods will facilitate their success in the clinical setting. PUBLIC HEALTH REVELANCE This project aims to develop new drug delivery systems for biomolecular drugs that must reach intracellular targets for efficacy. Biotherapeutics such as siRNA, antisense oligonucleotides (ODN), and proteins have significant therapeutic potential, but effectively formulating and delivering them remains a widely recognized challenge. Here we will develop smart polymeric carriers for siRNA drugs, and such carriers might be used widely for other DNA, RNA, and protein drugs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB002991-07
Application #
7822775
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Zullo, Steven J
Project Start
2003-09-19
Project End
2012-02-29
Budget Start
2010-03-01
Budget End
2011-02-28
Support Year
7
Fiscal Year
2010
Total Cost
$513,659
Indirect Cost
Name
University of Washington
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
Palanca-Wessels, Maria C; Booth, Garrett C; Convertine, Anthony J et al. (2016) Antibody targeting facilitates effective intratumoral siRNA nanoparticle delivery to HER2-overexpressing cancer cells. Oncotarget 7:9561-75
Wilson, John T; Postma, Almar; Keller, Salka et al. (2015) Enhancement of MHC-I antigen presentation via architectural control of pH-responsive, endosomolytic polymer nanoparticles. AAPS J 17:358-69
Lane, D D; Su, F Y; Chiu, D Y et al. (2015) Dynamic intracellular delivery of antibiotics via pH-responsive polymersomes. Polym Chem 6:1255-1266
Lane, D D; Chiu, D Y; Su, F Y et al. (2015) Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents. Polym Chem 6:1286-1299
Roy, Debashish; Berguig, Geoffrey Y; Ghosn, Bilal et al. (2014) Synthesis and characterization of transferrin-targeted chemotherapeutic delivery systems prepared via RAFT copolymerization of high molecular weight PEG macromonomers. Polym Chem 5:1791-1799
Keller, Salka; Wilson, John T; Patilea, Gabriela I et al. (2014) Neutral polymer micelle carriers with pH-responsive, endosome-releasing activity modulate antigen trafficking to enhance CD8(+) T cell responses. J Control Release 191:24-33
Palanca-Wessels, Maria Corinna; Press, Oliver W (2014) Advances in the treatment of hematologic malignancies using immunoconjugates. Blood 123:2293-301
Lundy, Brittany B; Convertine, Anthony; Miteva, Martina et al. (2013) Neutral polymeric micelles for RNA delivery. Bioconjug Chem 24:398-407
Wilson, John T; Keller, Salka; Manganiello, Matthew J et al. (2013) pH-Responsive nanoparticle vaccines for dual-delivery of antigens and immunostimulatory oligonucleotides. ACS Nano 7:3912-25
Cheng, Connie; Convertine, Anthony J; Stayton, Patrick S et al. (2012) Multifunctional triblock copolymers for intracellular messenger RNA delivery. Biomaterials 33:6868-76

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