Protocells: Mesoporous silica nanoparticle supported lipid bilayers for targeted delivery
Our group recently developed a new class of modular nanocarriers that synergistically combine features of mesoporous silica nanoparticles and liposomes. Fusion of liposomes (or native cell membranes) to a spherical, high-surface-area, mesoporous silica core followed by modification of the resulting supported lipid bilayer (SLB) with multiple copies of a targeting peptide, an endosomolytic peptide, and/or PEG results in a nanocarrier construct (the ‘protocell’) that, compared with liposomes improves on capacity, selectivity, and stability and enables targeted delivery and controlled release of high concentrations of multicomponent cargos (chemotherapeutic drugs, siRNA, etc.) within the cytosol or nucleus of cancer cells. Specifically, owing to its high surface area, the mesoporous silica core possesses a higher capacity for therapeutic and diagnostic agents than similarly sized liposomes. The fluid but stable SLB allows multivalent interactions with the target cell at very low targeting peptide densities, features crucial to maximizing specific binding, minimizing nonspecific binding, reducing dosage, and mitigating immunogenicity. Protocells were developed using an in vitro model. Recently we have developed an accessible ex ovo chick egg embryo model (the chorioallantoic membrane model), in which we can we image dynamic nanoparticle/cellular interactions at the individual nanoparticle scale within a complex fluid environment. CAM studies accelerate the translation of in vitro to in vivo. CAM studies along with in vivo fluorescence and radiolabeling studies (SPECT) reveal the requirement of achieving in vivo colloidal stability in order to avoid non-specific binding and to enable specific/targeted binding and drug delivery to individual circulating leukemia cells.
About the speaker
Jeff Brinker received his B.S., M.S., and Ph.D. degrees in Ceramic Science and Engineering at Rutgers University (1972-1978) and joined Sandia National Laboratories as a Member of the Technical Staff in 1979. In 2003 Brinker was appointed as the fifth Sandia National Laboratory Fellow (the highest technical position at Sandia – there have been only eight fellows over the sixty seven year history of the lab beginning with the Manhattan Project). He is currently Distinguished and Regent’s Professor of Chemical Engineering and Molecular Genetics and Microbiology, Co-Director of the Center for Micro-Engineered Materials, and Member of the Cancer Center at UNM, Fellow, Sandia National Laboratories, and Distinguished Affiliate Scientist at the Sandia/Los Alamos National Laboratories Center for Integrated Nanotechnologies (CINT). Over his thirty seven year career at Sandia and UNM, Brinker has made numerous pioneering contributions to processing, characterization, and understanding of porous and composite nanostructured materials and to the development of new classes of nanoparticle-based therapeutics for treatment of cancer and rare and infectious diseases.
Molecular Engineering and Sciences Seminar Series
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty.