Photo-inducible crosslinked nanoassemblies for pH-controlled drug release

Matthew Dickerson, Nickolas Winquist, Younsoo Bae

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Purpose: To control drug release from block copolymer nanoassemblies by variation in the degree of photo-crosslinking and inclusion of acid sensitive linkers. Methods: Poly(ethylene glycol)-poly(aspartate-hydrazide-cinnamate) (PEG-CNM) block copolymers were prepared and conjugated with a model drug, doxorubicin (DOX), through acid sensitive hydrazone linkers. The block copolymers formed photo-inducible, self-assembled nanoassemblies (piSNAs), which were used to produce photo-inducible crosslinked nanoassemblies (piCNAs) through UV crosslinking. The nanoassemblies were characterized to determine particle size, surface charge, pH- and crosslinking-dependent DOX release, in vitro cytotoxicity, and intracellular uptake as a function of photo-crosslinking degree. Results: Nanoassemblies with varying photo-crosslinking degrees were successfully prepared while retaining particle size and surface charge. Photo-crosslinking caused no noticeable change in DOX release from the nanoassemblies at pH 7.4, but the DOX-loaded nanoassemblies modulated drug release as a function of crosslinking at pH 6.0. The nanoassemblies showed similar cytotoxicity regardless of crosslinking degrees, presumably due to the low cellular uptake and cell nucleus drug accumulation. Conclusions: Photo-crosslinking is useful to control drug release from pH-sensitive block copolymer nanoassemblies as a function of crosslinking without altering the particle properties, and thus providing unique tools to investigate the pharmaceutical effects of drug release on cellular response.

Original languageEnglish
Pages (from-to)1254-1263
Number of pages10
JournalPharmaceutical Research
Issue number5
StatePublished - May 2014

Bibliographical note

Funding Information:
MD acknowledges the University of Kentucky Cancer Nanotechnology Training Center (UK-CNTC) postdoctoral traineeship, supported by the NCI/NIH and part of the National Cancer Institute Alliance for Nanotechnology in Cancer (5R25CA153954).


  • crosslinked nanoassemblies
  • drug carriers
  • drug delivery
  • nanoparticles
  • polymer micelles

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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