All-trans retinoic acid-encapsulated, CD20 antibody-conjugated poly(lactic-co-glycolic acid) nanoparticles effectively target and eliminate melanoma-initiating cells in vitro
Authors Chen X, Zhang Z, Yang S, Chen H, Wang D, Li J
Received 2 April 2018
Accepted for publication 12 August 2018
Published 25 September 2018 Volume 2018:11 Pages 6177—6187
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
Xingyu Chen,1,2 Zhiyuan Zhang,3 Shengfeng Yang,4 Hairong Chen,2 Dan Wang,5 Jun Li6
1Department of Dermatology and Venerology, Shandong University School of Medicine, Jinan, Shandong, 250000, China; 2Department of Dermatology, Qingdao Municipal Hospital, Qingdao, Shandong 266011, China; 3Department of Neurosurgery, Liaocheng People’s Hospital, Liaocheng, Shandong 252000, China; 4Department of Medical Oncology, Qingdao Center Hospital, Qingdao, Shandong 266011, China; 5Department of Ultrasound, Liaocheng People’s Hospital, Liaocheng, Shandong 252000, China; 6College of Pharmacy, Liaocheng University, Liaocheng, Shandong 252000, China
Purpose: Melanoma, which is initiated from melanocytes, is the most fatal type of skin cancer. Melanoma-initiating cells significantly contribute to the initiation, metastasis, and recurrence of melanoma, and CD20 is a marker of melanoma-initiating cells. All-trans retinoic acid (ATRA) has been demonstrated to induce differentiation, inhibit proliferation, and promote the apoptosis of cancer cells and cancer-initiating cells (CICs). However, there has been no report on ATRA activity against melanoma-initiating cells. In this study, we examined the activity of ATRA against melanoma-initiating cells and developed ATRA-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles, which were conjugated with a CD20 antibody (ATRA-PNP-CD20) for targeted delivery of ATRA to CD20+ melanoma-initiating cells.
Materials and methods: The effects of ATRA and ATRA-PNP-CD20 against melanoma-initiating cells were investigated using a cytotoxicity assay, tumorsphere formation assay, and flow cytometry.
Results: ATRA-PNP-CD20 had a size of 126.9 nm and a negative zeta potential. The drug-loading capacity of ATRA-PNP-CD20 was 8.7%, and ATRA-PNP-CD20 displayed a sustained release of ATRA for 144 hours. The results showed that ATRA-PNP-CD20 could effectively and specifically deliver ATRA to CD20+ melanoma-initiating cells, achieving superior inhibitory effects against CD20+ melanoma-initiating cells compared with those of free ATRA and nontargeted nanoparticles. To the best of our knowledge, we report for the first time a potent activity of ATRA against CD20+ melanoma-initiating cells, targeted drug delivery of ATRA via nanoparticles to melanoma-initiating cells, and the achievement of a superior inhibitory effect against melanoma-initiating cells by using a CD20 antibody.
Conclusion: ATRA-PNP-CD20 represents a promising tool for eliminating melanoma-initiating cells and shows a potential for the therapy of melanoma.
Keywords: melanoma, cancer-initiating cells, nanoparticles, CD20, antibody
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]