title: Anticancer drug-loaded multifunctional nanoparticles to enhance the chemotherapeutic efficacy in lung cancer metastasis.
abstract: BACKGROUND
  Inhalation of chemotherapeutic drugs directly into the lungs augments the drug exposure to lung cancers. The inhalation of free drugs however results in over exposure and causes severe adverse effect to normal cells. In the present study, epidermal growth factor (EGF)-modified gelatin nanoparticles (EGNP) was developed to administer doxorubicin (DOX) to lung cancers.
  
  
  RESULTS
  The EGNP released DOX in a sustained manner and effectively internalized in EGFR overexpressing A549 and H226 lung cancer cells via a receptor-mediated endocytosis. In vitro cytotoxicity assay showed that EGNP effectively inhibited the growth of A549 and H226 cells in a dose-dependent manner. In vivo biocompatibility study showed that both GNP and EGNP did not activate the inflammatory response and had a low propensity to cause immune response. Additionally, EGNP maintained a high therapeutic concentration in lungs throughout up to 24 h comparing to that of free drug and GNP, implying the effect of ligand-targeted tumor delivery. Mice treated with EGNP remarkably suppressed the tumor growth (~90% tumor inhibition) with 100% mice survival rate. Furthermore, inhalation of EGNP resulted in elevated levels of cleaved caspase-3 (apoptotic marker), while MMP-9 level significantly reduced comparing to that of control group.
  
  
  CONCLUSIONS
  Overall, results suggest that EGF surface-modified nanocarriers could be delivered to lungs via inhalation and controlled delivery of drugs in the lungs will greatly improve the therapeutic options in lung cancer therapy. This ligand-targeted nanoparticulate system could be promising for the lung cancer treatment.
authors.forename: Jian-Ting
authors.initials: JT
authors.lastname: Long
authors.forename: Tuck-Yun
authors.initials: TY
authors.lastname: Cheang
authors.forename: Shu-Yu
authors.initials: SY
authors.lastname: Zhuo
authors.forename: Rui-Fang
authors.initials: RF
authors.lastname: Zeng
authors.forename: Qiang-Sheng
authors.initials: QS
authors.lastname: Dai
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Li
authors.forename: Shi
authors.initials: S
authors.lastname: Fang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage*; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D004815:Epidermal Growth Factor; D004317:Doxorubicin; D066246:ErbB Receptors; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9