Cetuximab Combined With Sonodynamic Therapy Achieves Dual-Modal Image Monitoring for the Treatment of EGFR-Sensitive Non-Small-Cell Lung Cancer

Frontiers in Oncology

Zhonghai Wang¹  Xiangdong Li²  Lianfang Xue³  Lidong Liu⁴  Xiuxin Lu⁴  Guanhua Qiu⁴  Junjie Liu⁴  Xiaoqi Zhu⁴  Cuiqing Huang⁵ 

[1] Department of Guangxi Medical University, Affiliated Cancer Hospital, Nanning, China;Department of Oncology, Jinzhou Central Hospital, Jinzhou, China;Department of Pharmacy, The First Affiliated Hospital of Jinan University, Guangzhou, China;Department of Ultrasound and Department of Radiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China;The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Jinan University, Guangzhou, China;

关键词: NSCLC;    EGFR;    Cetuximab;    nanomaterials;    MRI;    IR780;   

DOI  :  10.3389/fonc.2022.756489

来源: DOAJ

【 摘 要 】

BackgroundBlocking signaling by epidermal growth factor receptor (EGFR), can effectively inhibit the proliferation and differentiation of non-small-cell lung cancer (NSCLC). Additionally, an increasing number of NSCLC patients have treatment limitations caused by EGFR overexpression or mutations. Therefore, we constructed a nanotherapy platform consisting of cetuximab (CTX) to target EGFR-sensitive NSCLC with an iron tetroxide core loading the sound-sensitive agent IR780 for dual-mode imaging diagnosis by combining targeting and sonodynamic therapy (SDT) to reshape the tumor microenvironment (TME), enhance the SDT antitumor effects and improve the therapeutic effects of EGFR sensitivity.MethodsIR780@INPs were prepared by reverse rotary evaporation, CTX was adsorbed/coupled to obtain IR780@INPs-CTX, and the morphology and structure were characterized. Intracellular ROS levels and cell apoptosis first verified its killing effects against tumor cells. Then, a nude mouse lung cancer subcutaneous xenograft model was established with HCC827 cells. A real-time fluorescence IVIS imaging system determined the targeting and live distribution of IR780@INPs-CTX in the transplanted tumors and the imaging effects of the T2 sequence of the INPs by magnetic resonance imaging (MRI) 0 h, 2 h, 4 h and 6 h after administration to confirm drug efficacy.ResultsIn vitro, US+IR780@INPs-CTX produced a large amount of ROS after SDT to induce cell apoptosis, and significant cell death after live/dead staining was observed. In vivo fluorescence imaging showed the IR780@INPs-CTX was mainly concentrated in the tumor with a small amount in the liver. MRI displayed rapid enrichment of the IR780@INPs into tumor tissue 0h after injection and the T2 signal intensity gradually decreases with time without obvious drug enrichment in the surrounding tissues. In vivo, at the end of treatment, the US+IR780@INPs-CTX group showed disappearance or a continued decrease in tumor volume, indicating strong SDT killing effects.ConclusionThe combination of CTX and SDT is expected to become a novel treatment for EGFR-sensitive NSCLC.

【 授权许可】

Unknown