title: Enhancement of cancer therapy efficacy by trastuzumab-conjugated and pH-sensitive nanocapsules with the simultaneous encapsulation of hydrophilic and hydrophobic compounds.
abstract: Trastuzumab-conjugated pH-sensitive double emulsion nanocapsules (DENCs) stabilized by a single-component Poly (vinyl alcohol) (PVA) with magnetic nanoparticles can be fabricated through a two-step double emulsion process; these nanocapsules can be used to encapsulate hydrophilic doxorubicin (Dox) and hydrophobic paclitaxel (PTX) simultaneously. When PMASH was attached to the shell of the DENCs, enhanced dual drug release of PTX/Dox was detected, specifically in intracellular acidic pH environments. The targeting ability of these Trastuzumab-conjugated DENCs was demonstrated with confocal images, which revealed a significantly elevated cellular uptake in HER-2 overexpressing SkBr3 cells. More importantly, an intravenous injection of this co-delivery system followed by magnetic targeting (MT) chemotherapy suppressed cancer growth in vivo more efficiently than the delivery of either PTX or Dox alone. The integration of the functionalities makes this combination therapy system a powerfully new tool for in vitro/in vivo cancer therapy, especially for in HER-2 positive cancers.
  
  
  BACKGROUND
  Trastuzumab-conjugated pH-sensitive nanocapsules were used in this study for simultaneous targeted delivery of hydrophobic (PTX) and hydrophilic (Dox) anti-cancer agents to HER-2 positive cancer cells. Additional use of magnetic targeting demonstrated superior efficacy of this delivery system compared to PTX or Dox alone.
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Chih-Sheng
authors.initials: CS
authors.lastname: Chiang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Shang-Hsiu
authors.initials: SH
authors.lastname: Hu
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Bang-Jie
authors.initials: BJ
authors.lastname: Liao
authors.affiliation: Department of Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Yuan-Ching
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Materials Sciences and Engineering, National Chiao Tung University, Hsinchu, Taiwan. Electronic address: sanyuanchen@mail.nctu.edu.tw.
authors.forename: San-Yuan
authors.initials: SY
authors.lastname: Chen
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D004655:Emulsions; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004317:Doxorubicin; D004655:Emulsions; D053769:Nanocapsules; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: Co-delivery; Emulsion; HER-2 positive breast cancer; Trastuzumab; pH sensitive