Journal
NATURE MATERIALS
Volume 10, Issue 5, Pages 389-397Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT2992
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Funding
- NIH/Roadmap for Medical Research [PHS 2 PN2 EY016570B]
- NCI [1U01CA151792-01]
- Air Force Office of Scientific Research [FA 9550-07-1-0054/9550-10-1-0054]
- US Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering
- Sandia National Laboratories' Laboratory Directed Research and Development (LDRD)
- National Security Science and Engineering at Sandia National Laboratories
- UCLA Center for Nanobiology and Predictive Toxicology (NIEHS) [1U19ES019528-01]
- NSF ERC Center for Environmental Implications of Nanotechnology at UCLA [NSF:EF-0820117]
- NSF [DGE-0504276, DGE-0549500, PREM/DMR 0611616]
- NSF at the University of New Mexico Center for Micro-Engineered Materials [DMR-0649132]
- NCRR
- University of New Mexico Health Sciences Center
- University of New Mexico Cancer Center
- US Department of Energy's National Nuclear Security Administration [DE-AC04-94AL85000]
- Div Of Biological Infrastructure
- Direct For Biological Sciences [0830117] Funding Source: National Science Foundation
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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. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. 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 10(6)-fold improvement over comparable liposomes.
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