title: Mesoporous silica nanoparticle nanocarriers: biofunctionality and biocompatibility.
abstract: The study of ordered mesoporous silica materials has exploded since their discovery by Mobil researchers 20 years ago. The ability to make uniformly sized, porous, and dispersible nanoparticles using colloidal chemistry and evaporation-induced self-assembly has led to many applications of mesoporous silica nanoparticles (MSNPs) as "nanocarriers" for delivery of drugs and other cargos to cells. The exceptionally high surface area of MSNPs, often exceeding 1000 m²/g, and the ability to independently modify pore size and surface chemistry, enables the loading of diverse cargos and cargo combinations at levels exceeding those of other common drug delivery carriers such as liposomes or polymer conjugates. This is because noncovalent electrostatic, hydrogen-bonding, and van der Waals interactions of the cargo with the MSNP internal surface cause preferential adsorption of cargo to the MSNP, allowing loading capacities to surpass the solubility limit of a solution or that achievable by osmotic gradient loading. The ability to independently modify the MSNP surface and interior makes possible engineered biofunctionality and biocompatibility. In this Account, we detail our recent efforts to develop MSNPs as biocompatible nanocarriers (Figure 1 ) that simultaneously display multiple functions including (1) high visibility/contrast in multiple imaging modalities, (2) dispersibility, (3) binding specificity to a particular target tissue or cell type, (4) ability to load and deliver large concentrations of diverse cargos, and (5) triggered or controlled release of cargo. Toward function 1, we chemically conjugated fluorescent dyes or incorporated magnetic nanoparticles to enable in vivo optical or magnetic resonance imaging. For function 2, we have made MSNPs with polymer coatings, charged groups, or supported lipid bilayers, which decrease aggregation and improve stability in saline solutions. For functions 3 and 4, we have enhanced passive bioaccumulation via the enhanced permeability and retention effect by modifying the MSNP surfaces with positively charged polymers. We have also chemically attached ligands to MSNPs that selectively bind to receptors overexpressed in cancer cells. We have used encapsulation of MSNPs within reconfigurable supported lipid bilayers to develop new classes of responsive nanocarriers that actively interact with the target cell. Toward function 4, we exploit the high surface area and tailorable surface chemistry of MSNPs to retain hydrophobic drugs. Finally, for function 5, we have engineered dynamic behaviors by incorporating molecular machines within or at the entrances of MSNP pores and by using ligands, polymers, or lipid bilayers. These provide a means to seal-in and retain cargo and to direct MSNP interactions with and internalization by target cells. Application of MSNPs as nanocarriers requires biocompatibility and low toxicity. Here the intrinsic porosity of the MSNP surface reduces the extent of hydrogen bonding or electrostatic interactions with cell membranes as does surface coating with polymers or lipid bilayers. Furthermore, the high surface area and low extent of condensation of the MSNP siloxane framework promote a high rate of dissolution into soluble silicic acid species, which are found to be nontoxic. Potential toxicity is further mitigated by the high drug capacity of MSNPs, which greatly reduces needed dosages compared with other nanocarriers. We anticipate that future generations of MSNPs incorporating molecular machines and encapsulated by membrane-like lipid bilayers will achieve a new level of controlled cellular interactions.
authors: Department of Chemical and Nuclear Engineering, the University of New Mexico, Albuquerque, NM 87131, USA.
authors: Derrick
authors: D
authors: Tarn
authors: Carlee E
authors: CE
authors: Ashley
authors: Min
authors: M
authors: Xue
authors: Eric C
authors: EC
authors: Carnes
authors: Jeffrey I
authors: JI
authors: Zink
authors: C Jeffrey
authors: CJ
authors: Brinker
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D008422:Materials Testing; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D012822:Silicon Dioxide
references: ACS Nano. 2009 Oct 27;3(10):3273-86
references: 19739605
references: J Am Chem Soc. 2010 Aug 11;132(31):10623-5
references: 20681678
references: ACS Nano. 2011 May 24;5(5):4131-44
references: 21524062
references: Small. 2009 Dec;5(23):2722-9
references: 19780070
references: Ann Occup Hyg. 1998 Jul;42(5):287-94
references: 9729916
references: Nat Rev Cancer. 2002 Jan;2(1):48-58
references: 11902585
references: Nanoscale. 2012 Jan 21;4(2):486-95
references: 22095171
references: Acc Chem Res. 2007 Sep;40(9):846-53
references: 17645305
references: ACS Nano. 2008 May;2(5):889-96
references: 19206485
references: Proc Natl Acad Sci U S A. 2011 Jul 5;108(27):10980-5
references: 21690347
references: J Am Chem Soc. 2009 Feb 4;131(4):1354-5
references: 19173660
references: J Phys Chem C Nanomater Interfaces. 2011 Oct 13;115(40):19496-19506
references: 23667713
references: Curr Opin Pulm Med. 2005 Mar;11(2):169-73
references: 15699791
references: Nature. 1966 Apr 16;210(5033):259-61
references: 4289018
references: Environ Health Perspect. 2000 Aug;108 Suppl 4:675-84
references: 10931786
references: Small. 2007 Aug;3(8):1341-6
references: 17566138
references: ACS Nano. 2011 Jul 26;5(7):5717-28
references: 21630682
references: J Am Chem Soc. 2012 Sep 26;134(38):15790-804
references: 22924492
references: J Environ Pathol Toxicol Oncol. 2001;20 Suppl 1:95-108
references: 11570678
references: Toxicol In Vitro. 2000 Oct;14(5):409-22
references: 10963957
references: Small. 2011 Jul 4;7(13):1816-26
references: 21595023
references: Nat Mater. 2011 May;10(5):389-97
references: 21499315
references: J Am Chem Soc. 2010 Sep 15;132(36):12690-7
references: 20718462
references: Chem Res Toxicol. 2010 Mar 15;23(3):620-9
references: 20085295
references: Cancer Res. 2002 Dec 15;62(24):7190-4
references: 12499256
references: Nature. 2000 May 4;405(6782):56-60
references: 10811215
references: ACS Nano. 2011 Jun 28;5(6):4434-47
references: 21563770
references: J Am Chem Soc. 2009 Aug 19;131(32):11344-6
references: 19624127
references: Biomaterials. 2008 Oct;29(30):4045-55
references: 18675454
references: ACS Nano. 2012 Mar 27;6(3):2174-88
references: 22309035
references: Chem Soc Rev. 2012 Apr 7;41(7):2590-605
references: 22216418
references: ACS Nano. 2010 Aug 24;4(8):4539-50
references: 20731437
references: Angew Chem Int Ed Engl. 2008;47(44):8438-41
references: 18726979
references: J Am Chem Soc. 2010 Apr 7;132(13):4834-42
references: 20230032
references: Small. 2009 Jan;5(1):57-62
references: 19051185
references: Nat Mater. 2009 Jul;8(7):543-57
references: 19525947
references: Acc Chem Res. 2011 Oct 18;44(10):903-13
references: 21675720
references: Small. 2008 Sep;4(9):1445-52
references: 18680095