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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