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

Journal of Nanobiotechnology

Shi Fang¹  He-Ping Li³  Qiang-Sheng Dai³  Rui-Fang Zeng³  Shu-Yu Zhuo¹  Tuck-yun Cheang²  Jian-Ting Long³ 

[1] Department of Clinical Nutrition, The First Affiliated Hospital, SUN Yat-Sen University, No. 58, cprZhongshan 2nd Road, Guangzhou 510080, Guangdong, China;Department of Vascular Surgery, The First Affiliated Hospital, SUN Yat-Sen University, Guangzhou 510080, China;Department of Medicinal Oncology, The First Affiliated Hospital, SUN Yat-Sen University, Guangzhou 510080, China

关键词: Controlled release;    Ligand targeting;    Inhalation;    Lung cancer;    Gelatin nanoparticles;    EGFR;    EGF;    Doxorubicin;   

Others  :  1139436
DOI  :  10.1186/s12951-014-0037-5

 received in 2014-08-15, accepted in 2014-09-04,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Long et al.; licensee BioMed Central Ltd.

【 图 表 】

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