title: In vitro and in vivo antitumor activity of a novel pH-activated polymeric drug delivery system for doxorubicin.
abstract: BACKGROUND
  Conventional chemotherapy agent such as doxorubicin (DOX) is of limited clinical use because of its inherently low selectivity, which can lead to systemic toxicity in normal healthy tissue.
  
  
  METHODS
  A pH stimuli-sensitive conjugate based on polyethylene glycol (PEG) with covalently attachment doxorubicin via hydrazone bond (PEG-hyd-DOX) was prepared for tumor targeting delivery system. While PEG-DOX conjugates via amid bond (PEG-ami-DOX) was synthesized as control.
  
  
  RESULTS
  The synthetic conjugates were confirmed by proton nuclear magnetic resonance (NMR) spectroscopy, the release profile of DOX from PEG-hyd-DOX was acid-liable for the hydrazone linkage between DOX and PEG, led to different intracellular uptake route; intracellular accumulation of PEG-hyd-DOX was higher than PEG-ami-DOX due to its pH-triggered profile, and thereby more cytotoxicity against MCF-7, MDA-MB-231 (breast cancer models) and HepG2 (hepatocellular carcinoma model) cell lines. Following the in vitro results, we xenografted MDA-MB-231 cell onto SCID mice, PEG-hyd-DOX showed stronger antitumor efficacy than free DOX and was tumor-targeting.
  
  
  CONCLUSIONS
  Results from these in vivo experiments were consistent with our in vitro results; suggested this pH-triggered PEG-hyd-DOX conjugate could target DOX to tumor tissues and release free drugs by acidic tumor environment, which would be potent in antitumor drug delivery.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Menglei
authors.initials: M
authors.lastname: Huan
authors.forename: Bangle
authors.initials: B
authors.lastname: Zhang
authors.forename: Zenghui
authors.initials: Z
authors.lastname: Teng
authors.forename: Han
authors.initials: H
authors.lastname: Cui
authors.forename: Jieping
authors.initials: J
authors.lastname: Wang
authors.forename: Xinyou
authors.initials: X
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Xia
authors.forename: Siyuan
authors.initials: S
authors.lastname: Zhou
authors.forename: Qibing
authors.initials: Q
authors.lastname: Mei
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D051379:Mice; D016513:Mice, SCID; D011092:Polyethylene Glycols / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D011092:Polyethylene Glycols; D004317:Doxorubicin