title: Synthesis, characterization, and in vivo efficacy evaluation of PGG-docetaxel conjugate for potential cancer chemotherapy.
abstract: OBJECTIVE
  This work is intended to develop and evaluate a biopolymeric poly(L-γ-glutamylglutamine) (PGG)-docetaxel (DTX) conjugate that can spontaneously self-assemble in aqueous solutions to become nanoparticles.
  
  
  METHODS
  DTX was covalently attached to hydrophilic PGG by direct esterification, and the conjugate was characterized by proton nuclear magnetic resonance spectroscopy, molecular weight gel permeation chromatography, solubility, size distribution and morphology, and hemolysis. Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. Dynamic light scattering, transmission electron microscopy, and atomic force microscopy revealed the particle size, distribution and morphology of the PGG-DTX conjugate. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460.
  
  
  RESULTS
  Conjugated DTX was found to have 2000 times improved water solubility compared with free DTX. The conjugate formed nanoparticles with an average diameter of 30 nm in spherical shape and unimodal particle size distribution. The conjugate exhibited about 2% hemolysis at 10 mg/mL, compared with 56% for Tween 80(®) at 0.4 mg/mL, and 33% for Cremophor EL(®) at 10 mg/mL. In addition, the conjugate was further tested for in vitro cytotoxicity and in vivo antitumor efficacy on the human non-small cell lung cancer cell line NCI-H460. As expected, conjugated DTX exhibited lower cytotoxicity compared to that of free DTX, in concentration-dependent manner. However, PGG-DTX showed better antitumor activity in NCI-H460 lung cancer-bearing mice with minimal weight loss compared to that of free DTX.
  
  
  CONCLUSIONS
  The PGG-DTX conjugate may be considered as an attractive and promising polymeric DTX conjugate for non-small cell lung cancer treatment.
authors.affiliation: Biomedical Engineering and Technology Institute, Institutes for Advanced Interdisciplinary Research, East China Normal University, Shanghai, People's Republic of China.
authors.forename: Danbo
authors.initials: D
authors.lastname: Yang
authors.forename: Sang
authors.initials: S
authors.lastname: Van
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Shu
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Liu
authors.forename: Yangfeng
authors.initials: Y
authors.lastname: Ge
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004151:Dipeptides / Q000737:chemistry*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D006461:Hemolysis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D058726:Nanoconjugates / Q000737:chemistry*; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D051381:Rats; D012995:Solubility; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology*; D015431:Weight Loss; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004151:Dipeptides; D004337:Drug Carriers; D058726:Nanoconjugates; D011108:Polymers; D043823:Taxoids; C047442:gamma-glutamylglutamine; D000077143:Docetaxel