title: Anti-tumor efficiency of paclitaxel and DNA when co-delivered by pH responsive ligand modified nanocarriers for breast cancer treatment.
abstract: BACKGROUND
  Combination of chemotherapy and nucleic acid therapy generally take advantage of drugs anti-tumor activity together with DNA capacity to transfect cancer cells, showing great promise in cancer treatment. However, effective co-delivery of drugs and DNA in a single carrier for cancer treatment remains a challenge.
  
  
  OBJECTIVE
  This study aimed to design a tumor targeted, pH sensitive nanocarriers for the co-delivery of gene and drug.
  
  
  METHODS
  Hyaluronic acid - acid sensitive linker - 1,2-distearoyl phosphatideylethanolamine copolymers (HA-as-DSPE) were synthesized. HA-as-DSPE modified, paclitaxel and pDNA loaded solid lipid nanoparticles (HA-PTX/pDNA SLN) was prepared. The physicochemical properties like morphology, size, and zeta potential as well as release properties were evaluated. The ability and therapeutic effects of the novel system for the co-delivery of PTX and pDNA were demonstrated in vitro and in vivo.
  
  
  RESULTS
  In vitro experiments and in vivo animal studies both confirmed that the HA-PTX/pDNA SLN system could promote the inhibition of tumor, at the same time deliver and transfect gene into the cancer cells.
  
  
  CONCLUSIONS
  Highest efficiency achieved by HA-PTX/pDNA SLN might result from the HA ligands that targeted the receptors on the cancer cells, the enhanced cellular uptake by the SLN formulations and also the pH sensitive bound of the carriers let the drug release more in the tumor cells. It could be concluded that HA-PTX/pDNA SLN could be used as a promising delivery system for drug and gene combination therapy.
authors: Department of Public Health, Shandong Jining No. 1 People's Hospital, Jining, 272011, Shandong, PR China.
authors: DongMei
authors: D
authors: Yu
authors: Department of Science Research, Shandong Jining No. 1 People's Hospital, Jining, 272011, Shandong, PR China.
authors: Wei
authors: W
authors: Li
authors: Department of Experimental Pathology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan, 250062, Shandong, PR China.
authors: Yueying
authors: Y
authors: Zhang
authors: Department of Oncology, Shandong Jining No. 1 People's Hospital, Jining, 272011, Shandong, PR China. Electronic address: hangbjnph@163.com.
authors: Bin
authors: B
authors: Zhang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D004337:Drug Carriers / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008024:Ligands; D004247:DNA; D017239:Paclitaxel
keywords: Breast cancer; Gene therapy; Hyaluronic acid; Solid lipid nanoparticles; pH sensitive carrier