Dual-Target Nanoparticle Reduces Lung Cancer Drug Resistance

This drug carrier nanoparticle specifically targets EGFR-mutant lung cancer cells and releases two types of drugs—doubling the effectiveness.

AsianScientist (May 26, 2016) – A team of scientists in China has designed a nanoparticle for efficiently overcoming drug resistance in lung cancer treatment. Crucially, it is dual-targeting, delivering two drugs—doxorubicin and gefitinib—for greater effectiveness. This work was published in Scientific Reports.

Epidermal growth factor receptor (EGFR) oncogenic mutation is frequently observed in non-small cell lung cancer (NSCLC) and is well-known as an ideal clinical therapeutic target. EGFR-targeted tyrosine kinase inhibitors are one class of lung cancer drugs. However, resistance to this kind of targeted drugs remains the main obstacle to successful targeted therapy in clinics after 6-12 months’ treatment.

Due to their unique properties, mesoporous SiO2 nanoparticles (MP-SiO2 NPs) have attracted substantial research interest in recent years. These properties include easy surface modification, or bioconjugation, for targeting; high drug-loading capability resulting from their large specific surface area and pore volume; and high biochemical and physicochemical stability.

Researchers led by Professor Ji Hongbin at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences designed a nanoparticle with dual targeting of EGFR-mutant cells using gefitinib-embedded, cetuximab-capped mesoporous silica. This nanomedicine is capable of efficiently inhibiting gefitinib-resistant tumor cell growth through the redox stimuli of glutathione.

Compared to MP-SiO2 NPs or a drug carrier loaded with either gefitinib or cetuximab alone, this dual-targeting nanomedicine could significantly inhibit the growth of gefitinib-resistant lung cancer cells in vitro and in vivo. This tumor suppression was due to the endocytosis of large amounts of nanomedicine and the effective gefitinib release induced by high glutathione levels in drug-resistant cancer cells.

Together, MP-SiO2 NPs and the cetuximab modification holds great potential for effectively delivering chemotherapeutic agents; both to inhibit the growth of the EGFR dysregulated lung cancer cells, and also overcome tyrosine kinase inhibitor resistance.

The article can be found at: Wang et al. (2016) Cetuximab-modified Mesoporous Silica Nano-medicine Specifically Targets EGFR-mutant Lung Cancer and Overcomes Drug Resistance.


Source: Shanghai Institutes for Biological Sciences.
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