title: Engineering multi-stage nanovectors for controlled degradation and tunable release kinetics.
abstract: Nanovectors hold substantial promise in abating the off-target effects of therapeutics by providing a means to selectively accumulate payloads at the target lesion, resulting in an increase in the therapeutic index. A sophisticated understanding of the factors that govern the degradation and release dynamics of these nanovectors is imperative to achieve these ambitious goals. In this work, we elucidate the relationship that exists between variations in pore size and the impact on the degradation, loading, and release of multistage nanovectors. Larger pored vectors displayed faster degradation and higher loading of nanoparticles, while exhibiting the slowest release rate. The degradation of these particles was characterized to occur in a multi-step progression where they initially decreased in size leaving the porous core isolated, while the pores gradually increased in size. Empirical loading and release studies of nanoparticles along with diffusion modeling revealed that this prolonged release was modulated by the penetration within the porous core of the vectors regulated by their pore size.
authors.affiliation: Department of Nanomedicine, The Methodist Hospital Research Institute, 6670 Bertner Ave., Houston, TX 77030, USA.
authors.forename: Jonathan O
authors.initials: JO
authors.lastname: Martinez
authors.forename: Ciro
authors.initials: C
authors.lastname: Chiappini
authors.forename: Arturas
authors.initials: A
authors.lastname: Ziemys
authors.forename: Ari M
authors.initials: AM
authors.lastname: Faust
authors.forename: Milos
authors.initials: M
authors.lastname: Kojic
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.forename: Mauro
authors.initials: M
authors.lastname: Ferrari
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
mesh_terms: D016503:Drug Delivery Systems / Q000379:methods*; D005434:Flow Cytometry; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D016062:Porosity; D045663:Quantum Dots; D012825:Silicon / Q000737:chemistry*
chemical_list: D012825:Silicon
keywords: Degradation; Drug delivery; Nanoparticle; Nanovector; Porosity; Porous silicon
references.citation: Biomaterials. 2008 Jan;29(3):377-84
references.pmid: 17936897
references.citation: J Biomech. 2009 Aug 25;42(12):1885-90
references.pmid: 19523635
references.citation: J Nanobiotechnology. 2008 Aug 15;6:9
references.pmid: 18702833
references.citation: Langmuir. 2004 Dec 7;20(25):11264-9
references.pmid: 15568884
references.citation: Biomaterials. 2008 Aug-Sep;29(24-25):3438-43
references.pmid: 18514306
references.citation: Biomed Microdevices. 2004 Sep;6(3):203-11
references.pmid: 15377829
references.citation: Nano Lett. 2006 Mar;6(3):543-7
references.pmid: 16522059
references.citation: J Pharm Sci. 2008 Feb;97(2):632-53
references.pmid: 17546667
references.citation: Cancer Res. 2010 May 1;70(9):3687-96
references.pmid: 20430760
references.citation: Nat Nanotechnol. 2010 Nov;5(11):815-21
references.pmid: 20972435
references.citation: Lab Chip. 2010 Nov 21;10(22):3074-83
references.pmid: 20697650
references.citation: Nat Nanotechnol. 2008 Mar;3(3):151-7
references.pmid: 18654487
references.citation: Ann Biomed Eng. 2008 Feb;36(2):254-61
references.pmid: 18172768
references.citation: Adv Healthc Mater. 2012 Jan 11;1(1):84-9
references.pmid: 23184690
references.citation: Adv Drug Deliv Rev. 2008 Aug 17;60(11):1266-77
references.pmid: 18508154
references.citation: Nat Nanotechnol. 2008 May;3(5):242-4
references.pmid: 18654511
references.citation: J Control Release. 2005 Nov 28;108(2-3):362-74
references.pmid: 16169628
references.citation: Philos Trans A Math Phys Eng Sci. 2006 Jan 15;364(1838):175-87
references.pmid: 18272459
references.citation: Biomaterials. 1996 Jan;17(2):103-14
references.pmid: 8624387
references.citation: Curr Opin Chem Biol. 2005 Aug;9(4):343-6
references.pmid: 15967706
references.citation: Biomaterials. 2009 May;30(15):2873-80
references.pmid: 19251317
references.citation: Chemphyschem. 2010 Apr 6;11(5):1029-35
references.pmid: 20162656
references.citation: Biomaterials. 2006 Oct;27(30):5307-14
references.pmid: 16797691
references.citation: Lab Chip. 2009 Jan 21;9(2):219-31
references.pmid: 19107277
references.citation: Clin Cancer Res. 2005 Oct 15;11(20):7532-7
references.pmid: 16243828
references.citation: Nat Mater. 2009 Apr;8(4):331-6
references.pmid: 19234444
references.citation: Tissue Eng Part A. 2008 Jan;14(1):195-206
references.pmid: 18333817
references.citation: Nat Rev Cancer. 2005 Mar;5(3):161-71
references.pmid: 15738981
references.citation: J Chem Phys. 2008 Apr 21;128(15):151102
references.pmid: 18433183
references.citation: Langmuir. 2008 Mar 18;24(6):2908-15
references.pmid: 18247639
references.citation: Expert Opin Drug Deliv. 2007 Mar;4(2):101-10
references.pmid: 17335408
references.citation: J Phys Chem B. 2010 Sep 2;114(34):11117-26
references.pmid: 20738139