TOMORROW, THURSDAY, 3/8/12 at 5:30 PM; Nano-Bio Seminar Series - Jeffrey Brinker, PhD - Lucile Packard Children’s Hospital, Freidenrich Auditorium

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Subject:	TOMORROW, THURSDAY, 3/8/12 at 5:30 PM; Nano-Bio Seminar Series - Jeffrey Brinker, PhD - Lucile Packard Children's Hospital, Freidenrich Auditorium
Date:	Wed, 07 Mar 2012 08:09:53 -0800
From:	Billie Robles <brobles@stanford.edu>
To:	nanoseminars@lists.stanford.edu, MIPS Seminars <mipsseminars@lists.stanford.edu>, Lucas Announcement <lucasannounce@lists.stanford.edu>

CCNE Nano-Bio Seminar Series

Presents

 

 

Jeffrey Brinker, PhD

Distinguished Professor

Sandia National Laboratories

Center for Micro-Engineered Materials

Department of Chemical Nuclear Engineering

The Cancer Research Center

University of New Mexico

Albuquerque, NM

 

Protocells: Mesoporous Silica Supported Lipid Bilayers for Targeted Delivery of Multicomponent Cargos to Cancer

 

Thursday, March 8, 2012

 

Seminar & Discussion: 5:30 pm – 6:30 pm

Lucile Packard Children's Hospital, Freidenrich Auditorium

http://www.lpch.org/DirectionsParking/InsideHospital/LPCH_1.html

 

Reception: 6:30 pm – 6:50 pm

Lobby of Freidenrich Auditorium

 

 

 

Abstract

 

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability, and a high capacity for disparate cargos. We recently developed a new class of hierarchical nanocarriers termed protocells that synergistically combine features of mesoporous silica nanoparticles and liposomes. Fusion of liposomes 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 PEG results in a nanocarrier construct (the 'protocell') that, compared with liposomes, the most extensively studied class of nanocarriers, improves on capacity, selectivity, and stability and enables targeted delivery and controlled release of high concentrations of multicomponent cargos (chemotherapeutic drugs, siRNA, dsDNA, toxins, etc.) within the cytosol or nucleus of cancer cells. Specifically, owing to its high surface area (>1000 square meters per gram), the mesoporous silica core possesses a higher capacity for therapeutic and diagnostic agents than similarly sized liposomes. Furthermore, owing to the substrate–membrane adhesion energy, the mesoporous silica core suppresses large-scale membrane bilayer fluctuations, resulting in greater stability than unsupported liposomal bilayers. In addition to conferring higher stability, the nanoporous support also results in enhanced lateral bilayer fluidity compared with that of either liposomes or SLBs formed on non-porous particles. We show the enhanced fluidity yet stability of the SLB enables dynamic reconfiguration of the surface allowing membrane bound ligands to engage in complex multivalent interactions with the target cell at very low targeting peptide densities. The synergistic combination of materials and biophysical properties organized over several hierarchical length scales enables high delivery efficiency and enhanced targeting specificity with a minimal number of targeting ligands, features crucial to maximizing specific binding, minimizing nonspecific binding, reducing dosage, and mitigating immunogenicity. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a million-fold improvement over comparable liposomes.

 

Sponsored by: Center for Cancer Nanotechnology Excellence and Translation (CCNE-T) Program - NIH/NCI U54

 

Hosted by: Dr. Sanjiv Sam Gambhir, Departments of Radiology & Bioengineering

 

--

Billie Robles

Department of Radiology

Stanford University School of Medicine

1201 Welch Road, Room P093

Stanford, CA 94305-5484

Tel: 650-736-0196

Fax: 650-736-7925