title: Photo-inducible crosslinked nanoassemblies for pH-controlled drug release.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone, Lexington, Kentucky, 40536-0596, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Dickerson
authors.forename: Nickolas
authors.initials: N
authors.lastname: Winquist
authors.forename: Younsoo
authors.initials: Y
authors.lastname: Bae
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D049329:Nanostructures; D011108:Polymers / Q000737:chemistry; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D000903:Antibiotics, Antineoplastic; D011108:Polymers; D004317:Doxorubicin