The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers

Carlee E. Ashley, Eric C. Carnes, Genevieve K. Phillips, David Padilla, Paul N. Durfee, Page A. Brown, Tracey N. Hanna, Juewen Liu, Brandy Phillips, Mark B. Carter, Nick J. Carroll, Xingmao Jiang, Darren R. Dunphy, Cheryl L. Willman, Dimiter N. Petsev, Deborah G. Evans, Atul N. Parikh, Bryce Chackerian, Walker Wharton, David S. PeabodyC. Jeffrey Brinker

Research output: Contribution to journalArticle

764 Scopus citations

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. 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 106-fold improvement over comparable liposomes.

Original languageEnglish (US)
Pages (from-to)389-397
Number of pages9
JournalNature Materials
Volume10
Issue number5
DOIs
StatePublished - May 2011

ASJC Scopus subject areas

  • Mechanical Engineering
  • Mechanics of Materials
  • Condensed Matter Physics
  • Materials Science(all)
  • Chemistry(all)

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    Ashley, C. E., Carnes, E. C., Phillips, G. K., Padilla, D., Durfee, P. N., Brown, P. A., Hanna, T. N., Liu, J., Phillips, B., Carter, M. B., Carroll, N. J., Jiang, X., Dunphy, D. R., Willman, C. L., Petsev, D. N., Evans, D. G., Parikh, A. N., Chackerian, B., Wharton, W., ... Brinker, C. J. (2011). The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers. Nature Materials, 10(5), 389-397. https://doi.org/10.1038/nmat2992