Cetuximab-modified CuS nanoparticles integrating near-infrared-II-responsive photothermal therapy and anti-vessel treatment

Bin Li,1 Zhongyin Jiang,1 Diya Xie,1 Yiqing Wang,1 Xingzhen Lao2 1Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing, Jiangsu Province 210093, China; 2Department of Microbial and Biochemical Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing , Jiangsu Province 210009, China Background: Photothermal therapy (PTT) has received extensive attention owing to its non-invasive nature and highly therapeutic outcomes. PTT agents and near-infrared (NIR) laser are essential elements in PTT. However, most PTT agents are composed of heavy metals, characterized by serious cytotoxicity and side effects, and NIR irradiation often damages normal tissue owing to the high dose, thus limiting the clinical application of PTT. Purpose: In this regard, exploring new perspectives enabling more PTT agents to be enriched into the tumor and NIR laser irradiation decay in PTT is vital. Methods: In this study, cetuximab (Ab), an anti-angiogenic antibody which targets the EGFR, was modified on CuS NPs (CuS-Ab NPs) to improve the aggregation of CuS NPs in the tumor. Results: The cellular uptake data and the biodistribution results showed comparable accumulation of CuS-Ab NPs in tumor, thus decreasing the cytotoxicity and side effects in normal tissues. More importantly, the modification of Ab in CuS-Ab NPs impressively inhibited the formation and progression of tumor vessels, as demonstrated by immunohistochemistry staining. The introduction of anti-vessel treatment requires CuS-Ab NPs to provide weak PTT, which means that a small amount of laser energy is required, inevitably causing negligible damage to normal tissue. Conclusion: Therefore, our tailor-made CuS-Ab NPs have promising potential in clinical applications. Keywords: photothermal therapy, CuS NPs, active targeting, cetuximab, EGFR, anti-angiogenesi