1. Radiotherapy-induced enrichment of EGF-modified doxorubicin nanoparticles enhances the therapeutic outcome of lung cancer
- Author
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Jing Wang, Yan Zhang, GuangPeng Zhang, Li Xiang, HaoWen Pang, Kang Xiong, Yun Lu, JianMei Li, Jie Dai, Sheng Lin, and ShaoZhi Fu
- Subjects
Lung Neoplasms ,Surface Properties ,Chemistry, Pharmaceutical ,Pharmaceutical Science ,Mice, Nude ,Apoptosis ,RM1-950 ,Mice ,Biomimetics ,Carcinoma, Non-Small-Cell Lung ,Animals ,Particle Size ,radiotherapy ,EGF ,Cell Proliferation ,Drug Carriers ,Mice, Inbred BALB C ,Antibiotics, Antineoplastic ,Epidermal Growth Factor ,technology, industry, and agriculture ,General Medicine ,Chemoradiotherapy ,Xenograft Model Antitumor Assays ,ErbB Receptors ,lung cancer ,Drug Liberation ,Doxorubicin ,Nanoparticles ,Therapeutics. Pharmacology - Abstract
Chemotherapy is the primary treatment for advanced non-small-cell lung cancer (NSCLC). However, related dose-dependent toxicity limits its clinical use. Therefore, it is necessary to explore new strategies for improving the clinical outcomes while reducing the side effects of chemotherapy in the treatment of NSCLC. In this study, we designed and synthesized epidermal growth factor (EGF)-modified doxorubicin nanoparticles (EGF@DOX-NPs) that selectively targets the epidermal growth factor receptor (EGFR) overexpressed in lung tumor cells. When administered in combination with low-dose X-ray radiotherapy (RT), the NPs preferentially accumulated at the tumor site due to radiation-induced outburst of the local intra-tumoral blood vessels. Compared with DOX alone, EGF@DOX-NPs significantly decreased the viability and migration and enhanced the apoptosis rates of tumor cells in vitro. Also, the EGF@DOX-NPs significantly inhibited tumor growth in vivo, increasing the survival of the tumor-bearing mice without apparent systemic toxic effects through RT-induced aggregation. The tumor cell proliferation was greatly inhibited in the RT + EGF@DOX-NPs group. Contrarily, the apoptosis of tumor cells was significantly higher in this group. These results confirm the promising clinical application of radiotherapy in combination with EGF@DOX-NPs for lung cancer treatment.
- Published
- 2022