title: Timed-release polymer nanoparticles.
abstract: Triggered-release of encapsulated therapeutics from nanoparticles without remote or environmental triggers was demonstrated in this work. Disassembly of the polymer nanoparticles to unimers at precise times allowed the controlled release of oligo DNA. The polymers used in this study consisted of a hydrophilic block for stabilization and second thermoresponsive block for self-assembly and disassembly. At temperatures below the second block's LCST (i.e., below 37 °C for in vitro assays), the diblock copolymer was fully water-soluble, and when heated to 37 °C, the polymer self-assembled into a narrow size distribution of nanoparticles with an average diameter of approximately 25 nm. The thermoresponsive nature of the second block could be manipulated in situ by the self-catalyzed degradation of cationic 2-(dimethylamino)ethyl acrylate (DMAEA) units to negatively charged acrylic acid groups and when the amount of acid groups was sufficiently high to increase the LCST of the second block above 37 °C. The disassembly of the nanoparticles could be controlled from 10 to 70 h. The use of these nanoparticles as a combined therapy, in which one or more agents can be released in a predetermined way, has the potential to improve the personal point of care treatment of patients.
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology and Institute for Molecular Biosciences, The University of Queensland, Brisbane, QLD 4072, Australia.
authors.forename: Nguyen T D
authors.initials: NT
authors.lastname: Tran
authors.forename: Nghia P
authors.initials: NP
authors.lastname: Truong
authors.forename: Wenyi
authors.initials: W
authors.lastname: Gu
authors.forename: Zhongfan
authors.initials: Z
authors.lastname: Jia
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Monteiro
mesh_terms: D000179:Acrylates / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008744:Methylamines / Q000737:chemistry; D053758:Nanoparticles; D012516:Osteosarcoma / Q000188:drug therapy; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism*
chemical_list: C509606:2-(dimethylamino ethyl)acrylate; D000179:Acrylates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008744:Methylamines; D011108:Polymers; D034741:RNA, Small Interfering; D004247:DNA