Anticancer drug-loaded multifunctional nanoparticles to enhance the chemotherapeutic efficacy in lung cancer metastasis

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• 作者：Jian-Ting Long (1)
  Tuck-yun Cheang (2)
  Shu-Yu Zhuo (3)
  Rui-Fang Zeng (1)
  Qiang-Sheng Dai (1)
  He-Ping Li (1)
  Shi Fang (3)
  
  1. Department of Medicinal Oncology ; The First Affiliated Hospital ; SUN Yat-Sen University ; Guangzhou ; 510080 ; China
  2. Department of Vascular Surgery ; The First Affiliated Hospital ; SUN Yat-Sen University ; Guangzhou ; 510080 ; China
  3. Department of Clinical Nutrition ; The First Affiliated Hospital ; SUN Yat-Sen University ; No. 58 ; cprZhongshan 2nd Road ; Guangzhou ; Guangdong ; 510080 ; China
  
• 关键词：Doxorubicin ; EGF ; EGFR ; Gelatin nanoparticles ; Lung cancer ; Inhalation ; Ligand targeting ; Controlled release
• 刊名：Journal of Nanobiotechnology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：12
• 期：1
• 全文大小：2,295 KB
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• 刊物类别：Chemistry and Materials Science
• 刊物主题：Biotechnology
  Nanotechnology
  
• 出版者：BioMed Central
• ISSN：1477-3155

文摘

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.