Main-chain degradable single-chain cyclized polymers as gene delivery vectors

Yongsheng Gao, Verona I. Böhmer, Dezhong Zhou, Tianyu Zhao, Wenxin Wang, Jos M.J. Paulusse*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

15 Citations (Scopus)

Abstract

Single-chain technology (SCT) allows the manipulation of polymeric architectures at an individual polymer chain level, providing a new platform for the fabrication of nanoscale polymeric objects. However, it remains problematic to apply this newborn technology to the biological and medical fields, since synthesis of single-chain polymeric nanoparticles relies heavily on controlled/living radical polymerization of vinyl based monomers, yielding a persistent non-degradable carbon-carbon based backbone. Moreover, the ultrahigh dilution conditions often required for single-chain polymer nanoparticle synthesis limits large-scale applicability. A versatile approach to achieve backbone degradability in single-chain cyclized polymers was developed by combining ring-opening addition polymerization and intramolecular cyclization into a one-pot RAFT copolymerization of cyclic and mono/multi-vinyl monomers system under concentrated conditions. The in situ intramolecular cyclization of individual propagating chains was achieved by kinetic control and statistical manipulation of mono- and multi-vinyl monomer copolymerization. The cyclic allylsulfide monomer 3-methylidene-1,9-dioxa-5,12,13-trithiacyclopentadecane-2,8-dione (MDTD) was copolymerized via the ring-opening pathway to introduce disulfide groups into the vinyl-based backbone without compromising the single chain propagation nature. Backbone degradable single chain polymeric nanoparticles were obtained with molecular weights of 10 kDa and MDTD incorporation ratios of 4.7%. Chemical degradation of the nanoparticles confirmed both their single chain nature, as well as backbone degradability. The single-chain cyclized polymeric nanoparticles were evaluated for their gene transfection capabilities. The backbone degradable nanoparticles displayed high transfection efficiencies and low cytotoxicities in both 3T3 and HeLa cells.
Original languageEnglish
Pages (from-to)375-383
JournalJournal of controlled release
Volume244
Issue numberPart B
DOIs
Publication statusPublished - 2016
Event14th European Symposium on Controlled Drug Delivery, ESCDD 2016 - Egmond aan Zee, Netherlands
Duration: 13 Apr 201515 Apr 2016
Conference number: 14

Keywords

  • Single chain technology
  • Radical ring opening polymerization
  • Degradability
  • Polymer nanoparticles
  • Gene delivery

Fingerprint Dive into the research topics of 'Main-chain degradable single-chain cyclized polymers as gene delivery vectors'. Together they form a unique fingerprint.

Cite this