title: Protocells: Modular Mesoporous Silica Nanoparticle-Supported Lipid Bilayers for Drug Delivery.
abstract: Mesoporous silica nanoparticle-supported lipid bilayers, termed 'protocells,' represent a potentially transformative class of therapeutic and theranostic delivery vehicle. The field of targeted drug delivery poses considerable challenges that cannot be addressed with a single 'magic bullet'. Consequently, the protocell has been designed as a modular platform composed of interchangeable biocompatible components. The mesoporous silica core has variable size and shape to direct biodistribution and a controlled pore size and surface chemistry to accommodate diverse cargo. The encapsulating supported lipid bilayer can be modified with targeting and trafficking ligands as well as polyethylene glycol (PEG) to effect selective binding, endosomal escape of cargo, drug efflux prevention, and potent therapeutic delivery, while maintaining in vivo colloidal stability. This review describes the individual components of the platform, including the mesoporous silica nanoparticle core and supported lipid bilayer, their assembly (by multiple techniques) into a protocell, and the combined, often synergistic, performance of the protocell based on in vitro and in vivo studies, including the assessment of biocompatibility and toxicity. In closing, the many emerging variations of the protocell theme and the future directions for protocell research are commented on.
authors.affiliation: Center for Micro-Engineered Materials, The University of New Mexico, Albuquerque, NM, 87131, USA.
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Butler
authors.affiliation: Department of Chemical and Biological Engineering, The University of New Mexico, Albuquerque, NM, 87131, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Durfee
authors.affiliation: Center for Micro-Engineered Materials, The University of New Mexico, Albuquerque, NM, 87131, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Theron
authors.affiliation: Bioenergy and Defense Technology Department, Sandia National Laboratories, Livermore, CA, 94551, USA.
authors.forename: Carlee E
authors.initials: CE
authors.lastname: Ashley
authors.affiliation: Nanobiology Department, Sandia National Laboratories, Livermore, California, 94551, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Carnes
authors.affiliation: Center for Micro-Engineered Materials, The University of New Mexico, Albuquerque, NM, 87131, USA.|Department of Chemical and Biological Engineering, The University of New Mexico, Albuquerque, NM, 87131, USA.|Advanced Materials Laboratory, Sandia National Laboratories, Albuquerque, New Mexico, 87185.
authors.forename: C Jeffrey
authors.initials: CJ
authors.lastname: Brinker
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002460:Cell Line; D003102:Colloids / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D008024:Ligands; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D016062:Porosity; D034741:RNA, Small Interfering / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry*; D014018:Tissue Distribution; D059016:Tumor Microenvironment
chemical_list: D001672:Biocompatible Materials; D003102:Colloids; D008024:Ligands; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D034741:RNA, Small Interfering; D011092:Polyethylene Glycols; D012822:Silicon Dioxide
keywords: drug delivery; mesoporous silica; nanoparticles; protocells; supported lipid bilayers; targeted delivery