The Targeted Delivery of Multicomponent Cargos to Cancer Cells via Nanoporous Particle-Supported Lipid Bilayers
By C. Ashley, Eric C. Carnes, Genevieve K. Phillips, D. Padilla, Paul N. Durfee, Page A. Brown, Tracey N. Hanna, Juewen Liu, Brandy Phillips, Mark B. Carter and 11 more. Nature Materials, 2011
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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 (HCC) exhibit a 10,000-fold greater affinity for HCC than for hepatocytes, endothelial cells, and immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, siRNA, 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 allow a single protocell loaded with a drug cocktail to kill a drug-resistant HCC cell, representing a 106-fold improvement over comparable liposomes.
Subfields: Biomaterials, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/16266f201d0d770ca126c8c8c89e0c2701d97cca
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Citations in the corpus
- Sol-gel based materials for biomedical applications (2016, background): “[531] fused supported lipid bilayers onto MSNs to construct a ‘‘protocell” (Fig.”
- Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy (2012, background): “bined the features of mesoporous silica particles and liposomes to address the multiple challenges of targeted delivery (Figure 6) [86].”
- Polymeric nanoparticles: Promising platform for drug delivery. (2017, background): “…PNPs can conquer complications accompanying the use of conventional anticancer remedies, including poor water solubility, quick elimination, and a deficient selectivity, causing a broad toxicity for normal tissues and decrease the anticancer amount reached the cancer tissues (Ashley et al., 2011).”