Development of EGFR-Targeting Nanomedicine for Effectively and Noninvasively Treats Lung Cancer Patients by Aerosol Delivery

Abstract

Lung cancer is a harmful form of cancer. The long-term survival rate of lung cancer patients treated by conventional modalities remains far from satisfactory. Encapsulated anticancer drugs in nanocarriers, can protect not only the integrity of drugs during transport but also the normal tissues from the toxicity. To develop an effective drug delivery system for lung cancer therapy, gelatin nanoparticles (GPs) were modified with NeutrAvidinFITC-biotinylated epidermal growth factor (bEGF) to form EGF receptor (EGFR)-seeking nanoparticles (GP-Av-bEGF). Cisplatin, a key drug used in the chemotherapy with sever side effect, was incorporated in the nanocarriers for active targeting to reduce toxicity. Furthermore, these nanocarriers were given to mice via inhalation of aerosol droplets which were generated by a nebulizer and delivered to mice model of lung cancer via aerosol. To summarize, the in vivo targeting ability of GP-Av-bEGF was examined by fluorescence images obtained from live mice showed that these nanoparticles could target the cancerous lungs in a more specific manner by aerosol delivery. And gelatin nanoparticles loaded with cisplatin and decorated with EGF tumor-specific ligand (GP-PtbEGF) were also successfully developed. Their in vitro and in vivo targeting ability and anticancer effect were confirmed. This treatment showed that GP-Pt-bEGF had stronger antitumor activity and was less toxic compared with other cisplatin formulas. Furthermore, these formulations were given to mice with lung cancer via aerosol delivery and showed that inhaled GP-Pt-bEGF could target EGFR-overexpressing cells to achieve high cisplatin dosage in cancerous lungs. The aerosol delivery of nanocarriers was demonstrated here. Simple aerosol delivery of targeted drug carriers may prove useful for the clinical treatment of lung cancer patients to eliminate patient complaints associated with the frequent intravenous injection.