title: Co-delivery of paclitaxel and TOS-cisplatin via TAT-targeted solid lipid nanoparticles with synergistic antitumor activity against cervical cancer.
abstract: BACKGROUND
  Cervical cancer is a major world health problem for women. Currently, cancer research focuses on improving therapy for cervical cancer using various treatment options such as co-delivery of chemotherapeutic agents by nanocarriers.
  
  
  OBJECTIVE
  The aim of this study was to develop trans-activating transcriptional activator (TAT)-modified solid lipid nanoparticles (SLNs) for co-delivery of paclitaxel (PTX) and α-tocopherol succinate-cisplatin prodrug (TOS-CDDP) (TAT PTX/TOS-CDDP SLNs) in order to achieve synergistic antitumor activity against cervical cancer.
  
  
  METHODS
  Lipid prodrug of CDDP (TOS-CDDP) and TAT-containing polyethylene glycol-distearoyl-phosphatidylethanolamine (TAT-PEG-DSPE) were synthesized. TAT PTX/TOS-CDDP SLNs were prepared by emulsification and solvent evaporation method. Physicochemical characteristics of SLNs such as size, morphology, and release profiles were explored. In vitro and in vivo studies were carried out to assess the efficacy of their antitumor activity in target cells.
  
  
  RESULTS
  TAT PTX/TOS-CDDP SLNs could be successfully internalized by HeLa cells and showed a synergistic effect in the suppression of cervical tumor cell growth. They exhibited high tumor tissue accumulation, superior antitumor efficiency, and much lower toxicity in vivo.
  
  
  CONCLUSIONS
  The present study indicates that the co-delivery system provides a promising platform as a combination therapy for the treatment of cervical cancer, and possibly other types of cancer as well.
authors.affiliation: Department of Internal Medicine Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Ji'nan, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Ji'nan, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Internal Medicine Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Ji'nan, People's Republic of China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Internal Medicine Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Ji'nan, People's Republic of China.
authors.forename: Shumei
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Internal Medicine Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Ji'nan, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Ji'nan, People's Republic of China.
authors.forename: Lixi
authors.initials: L
authors.lastname: Jiang
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D002945:Cisplatin / Q000008:administration & dosage; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D008055:Lipids; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D008055:Lipids; D010714:Phosphatidylethanolamines; D011355:Prodrugs; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols; D024502:alpha-Tocopherol; D017239:Paclitaxel; D002945:Cisplatin
keywords: cell-penetrating peptide; cervical cancer; combination therapy; lipid-based prodrug; solid lipid nanoparticles