Degradable-brushed pHEMA-pDMAEMA synthesized via ATRP and click chemistry for gene delivery

Xulin Jiang, Martin C. Lok, Wim E. Hennink

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Brushed polymers composed of a backbone of poly(hydroxyethyl methacrylate) (pHEMA) onto which poly(2-(dimethylamino)ethyl methacrylate)s (pDMAEMAs) was grafted via a hydrolyzable linker were synthesized and evaluated as nonviral gene delivery vectors. Both pDMAEMA and pHEMA polymers with controlled molecular weights and narrow distributions were synthesized by controlled atom transfer radical polymerization (ATRP). The azide initiator was used to ensure complete and monoazide functionalization of the pDMAEMA polymer chains. Click reaction between pHEMA with alkyne side groups and the azide end group in the pDMAEMA resulted in a high-molecular-weight polymer composed of low-molecular-weight constituents via an easily degradable carbonate ester linker. The length of the pDMAEMA grafts as well as the number of grafts of the brushed pHEMA-pDMAEMA can be easily varied. At physiological conditions (pH 7.4 and 37°C), the brushed polymer degraded by hydrolysis of the carbonate ester with a half-life of 96 h. The molecular weights of the formed degradation products was very close to that of the starting pDMAEMA, which is likely below the renal excretion limit (
Original languageEnglish
Pages (from-to)2077-2084
Number of pages8
JournalBioconjugate Chemistry
Volume18
Issue number6
DOIs
Publication statusPublished - 2007

Keywords

  • cation
  • interferon
  • interferon 7
  • nanoparticle
  • plasmid DNA
  • poly[2 (dimethylamino)ethyl methacrylate]
  • polymacon
  • unclassified drug
  • acidity
  • animal cell
  • article
  • atom transfer radical polymerization
  • biodegradability
  • chemistry
  • comparative study
  • controlled study
  • cytotoxicity
  • DNA structure
  • drug synthesis
  • gene vector
  • genetic transfection
  • half life time
  • hydrolysis
  • hydrophilicity
  • molecular weight
  • nonhuman
  • nonviral gene delivery system
  • polymerization
  • reaction analysis
  • temperature dependence

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