MRP1-targeted near infrared photoimmunotherapy for drug resistant small cell lung cancer
| Autor: | Stacy Yeh, Fang Li, Yao Sun, Chengqiong Mao, Junbo Xin, Xin Ming, Qin Shi |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Lung Neoplasms
Infrared Rays medicine.drug_class Pharmaceutical Science 02 engineering and technology Drug resistance Monoclonal antibody 030226 pharmacology & pharmacy Mice 03 medical and health sciences 0302 clinical medicine Multidrug Resistance Protein 1 In vivo Cell Line Tumor medicine Animals Humans ATP Binding Cassette Transporter Subfamily B Member 1 Prospective Studies Photosensitizing Agents biology business.industry Photoimmunotherapy Phototherapy 021001 nanoscience & nanotechnology Small Cell Lung Carcinoma Xenograft Model Antitumor Assays Pharmaceutical Preparations Apoptosis Cancer cell biology.protein Cancer research Immunotherapy Antibody 0210 nano-technology business |
| Zdroj: | International Journal of Pharmaceutics. 604:120760 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2021.120760 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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