title: Nanoparticle Formation from Hybrid, Multiblock Copolymers of Poly(Acrylic Acid) and VPGVG Peptide.
abstract: Elastin-mimetic hybrid copolymers with an alternating molecular architecture were synthesizedviathe step growth polymerization of azide-functionalized, telechelic poly(tert-butyl acrylate) (PtBA) and an alkyne-terminated, valine and glycine-rich peptide with a sequence of (VPGVG)2(VG2). The resultant hybrid copolymer, [PtBA-VG2]n, contains up to six constituent building blocks and has a polydispersity index (PDI) of ~1.9. Trifluoroacetic acid (TFA) treatment of [PtBA-VG2]ngave rise to an alternating copolymer of poly(acrylic acid) (PAA) and VG2 ([PAA-VG2]n). The modular design permits facile adjustment of the copolymer composition by varying the molecular weight of PAA (22 and 63 repeat units). Characterization by dynamic light scattering indicated that the multiblock copolymers formed discrete nanoparticles at room temperature in aqueous solution at pH 3.8, with an average diameter of 250-270 nm and a particle size distribution of 0.34 for multiblock copolymers containing PAA22and 0.17 for those containing PAA63. Upon increasing the pH to 7.4, both types of particles were able to swell without being disintegrated, reaching an average diameter of 285-300 nm for [PAA22-VG2]nand 330-350 nm for [PAA63-VG2]n, respectively. The nanoparticles were not dissociated upon the addition of urea, further confirming their unusual stability. The nanoparticles were capable of sequestering a hydrophobic fluorescent dye (pyrene), and the critical aggregation concentration (CAC) was determined to be 1.09 × 10-2or 1.05 × 10-2mg/mL for [PAA22-VG2]nand [PAA63-VG2]n, respectively. We suggest that the multiblock copolymers form through collective H-bonding and hydrophobic interactions between the PAA and VG2 peptide units, and that the unusual stability of the multiblock nanoparticles is conferred by the multiblock architecture. These hybrid multiblock copolymers are potentially useful as pH-responsive drug delivery vehicles, with the possibility of drug loading through concerted H-bonds and hydrophobic interactions.
authors: Department of Materials Science and Engineering, Delaware Biotechnology Institute, University of Delaware, Newark, DE 19716, USA.
authors: Sarah E
authors: SE
authors: Grieshaber
authors: Bradford A
authors: BA
authors: Paik
authors: Shi
authors: S
authors: Bai
authors: Kristi L
authors: KL
authors: Kiick
authors: Xinqiao
authors: X
authors: Jia
references: Biomacromolecules. 2011 Feb 14;12(2):269-89
references: 21235251
references: Biomacromolecules. 2009 Oct 12;10(10):2740-9
references: 19743840
references: Acta Biomater. 2008 Jul;4(4):827-37
references: 18178532
references: J Am Chem Soc. 2009 Jul 8;131(26):9304-10
references: 19527028
references: J Am Chem Soc. 2003 Dec 10;125(49):15059-64
references: 14653740
references: Soft Matter. 2010 Nov 7;6(21):5293-5297
references: 21278815
references: Chem Soc Rev. 2011 May;40(5):2475-93
references: 21229168
references: J Am Chem Soc. 2001 Jun 6;123(22):5231-9
references: 11457385
references: Pharm Res. 1999 May;16(5):597-600
references: 10349998
references: Eur J Biochem. 1998 Nov 15;258(1):1-18
references: 9851686
references: Philos Trans R Soc Lond B Biol Sci. 2002 Feb 28;357(1418):169-84
references: 11911774
references: J Chem Phys. 2008 Apr 28;128(16):164906
references: 18447499
references: Soft Matter. 2007 Mar 20;3(4):394-408
references: 32900058
references: Biomacromolecules. 2011 Jan 10;12(1):247-52
references: 21158387
references: J Mol Biol. 1998;283(1):255-64
references: 9761688
references: Langmuir. 2004 May 11;20(10):3894-900
references: 15969376
references: J Am Chem Soc. 2001 Dec 5;123(48):11991-8
references: 11724607
references: J Control Release. 2005 Dec 5;109(1-3):169-88
references: 16289422
references: Biopolymers. 2010;94(1):32-48
references: 20091878
references: Biomacromolecules. 2011 Oct 10;12(10):3499-507
references: 21866922
references: Biomaterials. 2008 Feb;29(6):625-32
references: 18006054
references: Macromolecules. 2009 Apr;42(7):2532-2541
references: 19763157
references: Biomacromolecules. 2012 Jun 11;13(6):1774-86
references: 22533503
references: React Funct Polym. 2011 Mar 1;71(3):294-302
references: 21499527
references: Biomacromolecules. 2006 Aug;7(8):2415-9
references: 16903690
references: Macromol Chem Phys. 2011 Feb 1;212(3):229-239
references: 21359141
references: Macromolecules. 2011 Mar 4;44(7):1942-1951
references: 21552373
references: Biomacromolecules. 2011 Jun 13;12(6):2184-92
references: 21553871
references: Macromol Rapid Commun. 2009 Feb 18;30(4-5):267-77
references: 21706604