Mary Napier, PhD


HONORS & AWARDS

  • 2012 – Massey Award for Distinguished Service


RESEARCH

Summary:

The delivery of therapeutics and imaging agents for the diagnosis and treatment of disease has improved dramatically over the years with the development of nano-carriers such as liposomes, micelles, dendrimers, polymer particles, and colloidal precipitates. These nanostructures are derived from “bottom-up” chemical approaches, which yield heterogeneous structures with little capability for the rational design of effective vectors. The inability to simultaneously and comprehensively address several significant design criteria for effective delivery vectors has limited such bottom-up delivery technologies from reaching full clinical promise. We have developed a templated, top down particle fabrication method called PRINT® (Particle Replication In Non-wetting Templates) which is a novel method for the molding of shape-specific particles at the nanometer scale. The technique was developed by DeSimone and coworkers at the University of North Carolina at Chapel Hill, offers an unprecedented opportunity to study the challenges associated with nanoparticle delivery and, more importantly, offers a versatile platform to engineer solutions to these problems. The PRINT advantage is the ability to generate “calibration quality” nanoconstructs that are able to precisely control the geometric (size, shape), surface (zeta potential, stealthing ligands), cargo encapsulation and release (chemotherapeutics, oligonucleotides, proteins, siRNA, RNA, imaging agents), surface chemistries (antibodies, PEG chains, metal chelators), including the spatial distribution of ligands on the particle surface and deformability characteristics so as to engineer the optimal drug delivery vehicle. PRINT allows for the study of the relationships between specific physical parameters of the particles and biodistribution, bioavailability, pharmacokinetics and therapeutic efficacy for a range of medical applications.

The group is focused on multiple research areas, including delivery of chemotherapeutics using GEM, otrthotopic and xenograft murine models of lung, breast, pancreatic cancer, the co-delivery of adjuvants and antigens for vaccines, delivery of antibiotics for the treatment of UTIs, blood substitutes and pulmonary delivery.


REPRESENTATIVE PUBLICATIONS

  • J. Xu, J. Wang, J.C. Luft, S. Tian, G. Owens, B.W. Maynor, M.E. Napier,  J.M. DeSimone,  Rendering Protein-based Particles Transiently Insoluble for Therapeutic Applications, JACS, accepted, in press.
  • M.C. Parrott, M.C Finniss, J.C. Luft, A. Pandya, A. Gullapalli, M.E. Napier, J.M DeSimone, Incorporation and Controlled Release of Silyl Ether Prodrugs from PRINT Nanoparticles, JACS, accepted, in press.
  • S.S. Dunn, S. Tian, S. Blake, J. Wang, A.L. Galloway, A. Murphy, P.D. Pohlhaus, J.P. Rolland, M.E. Napier, J. M. DeSimone, Reductively Responsive siRNA-Conjugated Hydrogel Nanoparticles for Gene Silencing, JACS, accepted, in press.
  • W. Hasan, K. Chu, A. Gullapalli, S.S. Dunn, E.M. Enlow, J.C. Luft, S. Tian, M.E. Napier, P.D. Pohlhaus, J.P. Rolland, J.M. DeSimone, Delivery of Multiple siRNAs Using Lipid-Coated PLGA Nanoparticles for Treatment of Prostate Cancer, Nano Letters, 12 (2012) 287-292.
  • M.E. Werner, J.A. Copp, S. Karve, N.D. Cummings, R. Sukumar, C.X. Li, M.E. Napier, R.C. Chen, A.D.  Cox, A.Z. Wang, ACS NANO, 5(11) (2011) 8990-8998.
  • J.L. Perry, K.P. Herlihy, M.E. Napier, J.M. DeSimone, PRINT: A Novel Platform Toward Shape and Size Specific Nanoparticle Theranostics, Acc. of Chem. Res., 44(10) (2011) 990-998.
  • J. Wang, J.D. Byrne, M.E. Napier, J.M. DeSimone, More Effective Nanomedicines through Particle Design, Small, 7(14) (2011) 1919-1931.
  • J. Pillai, S.S. Dunn, M.E. Napier, J.M. DeSimone, Novel platforms for vascular carriers with controlled geometry, IUBMB 63(8) (2011) 596-606.
  • E.M. Enlow, J.C. Luft, M.E. Napier, J.M. DeSimone, Potent Engineered PLGA Nanoparticles by Virtue of Exceptionally High Chemotherapeutic Loadings, Nano Letters, 11(2) (2011) 808–813.
  • T.J. Merkel, S.W. Jones, K.P. Herlihy, F.R. Kersey, A.R. Shields, M.E. Napier, A. Z. Wang, J. E. Bear, J.M. DeSimone, Using Mechano-biological Mimicry to Extend Circulation Times of Red Blood Cell Replicas, Proceedings of the National Academy of Sciences, 108(2) (2011) 586-591.
  • M.C. Parrott, J.C. Luft, J.D. Byrne, J.H. Fain, M.E. Napier, J.M. DeSimone, Tunable Bi-functional Silyl Ether Cross-Linkers for the Design of Acid Sensitive Biomaterials,  J. Am. Chem. Soc. 132(50) (2010) 17928-17932.
  • A.L. Galloway, A. Murphy, J.P. Rolland, K.P. Herlihy, R.A. Petros, M.E. Napier, J. M. DeSimone, Micromolding for the Fabrication of Biological Microarrays in Biological Microarrays: Methods and Protocols, Methods in Molecular Biology, vol. 671, edited by Ali Khademhosseini et al.,2010 Springer Science+Business Media, LLC.
  • S. Tian, J. Wang, R.A. Petros, M.E. Napier, J.M. DeSimone, The Complex Role of Multivalency in Nanoparticles Targeting the Transferrin Receptor for Cancer Therapies, JACS 132 (2010) 11306.
  • J.F. Campbell, M.E. Napier, S.W. Feldberg, H.H. Thorp, Metal-Mediated Electrochemical Oxidation of DNA-Wrapped Carbon Nanotubes, Journal of Physical Chemistry B 114 (2010) 8861-8870
  • W. Jeong, M.E. Napier, J.M. DeSimone, Challenging Nature’s Monopoly on the Creation of Well-Defined Nanoparticles, Nanomedicine 5 (2010) 633.
  • S.E.A. Gratton, P.A. Ropp, P.D. Pohlhaus, J.C. Luft, V.J. Madden, M.E. Napier, J.M. DeSimone, The Effect of Particle Design on Cellular Internalization Pathways, PNAS 105 (2008) 11613-11618.

CONTACT INFO

237 Caudill
Chapel Hill, NC 27599

Office: 919-962-6303

mnapier@unc.edu