TOMORROW, THURSDAY, 3/8/12 at 5:30 PM; Nano-Bio Seminar Series - Jeffrey Brinker, PhD - Lucile Packard Children’s Hospital, Freidenrich Auditorium
Roger T. Howe
rthowe at stanford.edu
Wed Mar 7 08:17:53 PST 2012
-------- Original Message --------
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 at stanford.edu>
To: nanoseminars at lists.stanford.edu, MIPS Seminars
<mipsseminars at lists.stanford.edu>, Lucas Announcement
<lucasannounce at 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 nanoparticlesand liposomes. Fusion of liposomes to a spherical,
high-surface-area, mesoporous silica corefollowed 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
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