期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 604, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120760
关键词
Near infrared photoimmunotherapy (NIR-PIT); Multidrug resistance protein 1 (MRP1); Drug-resistant small cell lung cancer; Targeted photodynamic therapy
资金
- Natural Science Foundation of Jiangsu Province [BK20180273]
- Qing-Lan Project of Jiangsu Colleges, Jiangsu Overseas Research & Training Program for University Prominent Professors
- Scientific & Technological Innovation Team Project of Jiangsu Vocational College of Medicine [20188103]
This study demonstrates that the anti-MRP1 antibody (Mab)-IR700 conjugate shows higher cellular delivery in multidrug resistant SCLC cells, leading to a stronger photokilling effect and tumor suppression.
Small cell lung cancer (SCLC), one of the most aggressive cancers, has a high mortality rate and poor prognosis, and the clinical therapeutic outcomes of multidrug resistant SCLC are even worse. Multidrug resistance protein 1 (MRP1), one of the ATP-binding cassette (ABC) transporter proteins that cause decreased drug accumulation in cancer cells, is overexpressed in drug resistant SCLC cells and could be a promising target for treating the patients suffering from this illness. Near infrared photoimmunotherapy (NIR-PIT) is a newly developed approach for targeted cancer treatment which uses a conjugate of a monoclonal antibody and photoabosorber IR700 followed by NIR light irradiation to induce rapid cancer cell death. In the present study, an anti-MRP1 antibody (Mab)-IR700 conjugate (Mab-IR700) was synthesized, purified and used to treat chemoresistant SCLC H69AR cells that overexpressed MRP1, while non-MRP1-expressing H69 cells were used as a control. Then, the photokilling and tumor suppression effect were separately evaluated in H69AR cells both in vitro and in vivo. Higher cellular delivery of Mab-IR700 was detected in H69AR cells, whereas there was little uptake of IgG-IR700 in both H69 and H69AR cells. Due to the targeting activity of Mab, stronger photokilling effect was found both in H69AR cells and spheroids treated with Mab-IR700, while superior tumor suppression effect was also observed in the mice treated with Mab-IR700 and light illumination. Photoacoustic imaging results proved that oxygen was involved in NIR-PIT treatment, and TUNEL staining images showed the occurrence of cell apoptosis, which was also testified by HE staining. This research provides MRP1 as a novel target for PIT and presents a prospective way for treating drug resistant SCLC and, thus, should be further studied.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据