To improve current therapeutic nano-technology using, 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) of Chinese Academy of Sciences (CAS) has successfully designed a nanoparticle with doxorubicin and gefitinib loaded cetuximab-capped mesoporous silica for efficiently overcoming drug resistance of EGFR-TKI in lung cancer. This study has been published in Scientific Reports.

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

Due to their unique properties, mesoporous SiO₂ nanoparticles (MP-SiO₂ NPs) attract 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, facile tuning of the particle size over a broad range, high biochemical and physicochemical stability, etc.

Researchers designed 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 a good method to specifically and effectively deliver the EGFR-TKIs and overcome drug resistance. 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 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.

Figure: A scheme of the synthesis of drug-loaded cetuximab-capped MP-SiO₂ NP (Image by Prof. JI Hongbin 's lab)