To improve current therapeutic using nano-technology, a team of scientists led by Prof. JI Hongbin and ZHANG Zhanxia at the Institute of Biochemistry and Cell Biology (SIBCB), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences(CAS), have designed a cetuximab-capped mesoporous silica nanoparticle as the drug carrier to specifically target EGFR-mutant lung cancer cells and efficiently release loaded chemotherapeutic agent including doxorubicin and gefitinib to overcome TKIs resistance. This work was recently published in Scientific Reports.
Epidermal growth factor receptor (EGFR) oncogenic mutation is frequently observed in non-small cell lung cancer (NSCLC) and well recognized as an effective therapeutic target in clinic. There are mainly two categories of targeted drugs for EGFR-mutated lung cancer. One is EGFR-targeted tyrosine kinase inhibitors (TKIs), including gefitinib (GEF) and erlotinib. The other is anti-EGFR monoclonal antibody, such as cetuximab (CET). However, drug resistance to these therapeutic reagents is the main obstacle to successful targeted therapy in clinic after 6-12 months’ treatment.
Mesoporous SiO2 nanoparticles (MP-SiO2 NPs) attract substantial research interest in recent years due to its unique properties, such as high drug loading capability resulting from their large specific surface area and pore volume, facile tuning of the particle size over a broad range, easy surface modification or bioconjugation for targeting, and high biochemical and physicochemical stability. These properties of MP-SiO2 NP were implemented to develop new drug delivery systems, catalysts and imaging materials.
To improve current therapeutic using nano-technology, they design a novel nano-particle with dual targeting of EGFR-mutant cells using gefitinib-embedded cetuximab-capped mesoporous silica. This mesoporous silica nano-medicine has the capability to efficiently inhibit GEF-resistant tumor cell growth through the redox stimuli of glutathione (GSH). Compared to MP-SiO2 NPs or the drug carrier loaded with either gefitinib or cetuximab alone, this dual-targeting nano-medicine could significantly inhibit the growth of GEF-resistant lung cancer cells in vitro and in vivo. This tumor suppression was due to the endocytosis of large amount of nano-medicine and the effective gefitinib release induced by high glutathione level in drug-resistant cancer cells. This design might serve as good method to specifically and effectively deliver the EGFR-TKIs and overcome drug resistance.
Together, the platform of the MP-SiO2 NPs and the cetuximab modification has great potential for effective delivering chemotherapeutic agent to inhibit the growth of the EGFR dysregulated lung cancer cells that can be used to overcome TKIs resistance.
This work entitled “Cetuximab-modified mesoporous silica nano-medicine specifically targets EGFR-mutant lung cancer and overcomes drug resistance” was published online in Scientific Reports on May 6, 2016.
This work was supported by the National Basic Research Program of China, the National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, the “cross and cooperation in science and technology innovation team” program and Shanghai Institutes for Biological Sciences.
CONTACT:
JI Hongbin, Institutions of Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200031, China.
Email:hbji@sibcb.ac.cn
Figure. A scheme of the synthesis of drug-loaded cetuximab-capped MP-SiO2 NP (Image provided by Prof. JI Hongbin’s lab).
KEYWORDS: mesoporous silica nano-medicine, drug resistance, EGFR-TKI, cetuximab, redox
NEWS ABSTRACT:
The nano-medicine cetuximab-capped gefitinib-loaded mesoporous SiO2 nanoparticles (MP-SiO2 NP) shows great anti-tumor efficacy in treatment of gefitinib-resistant lung cancer cells in vitro and in vivo. The tumor suppression is largely due to the specific dual-targeting feature of this nano-medicine. Such design might serve as a good method to specifically and effectively deliver the EGFR-TKIs and overcome drug resistance.
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