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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

DOI https://doi.org/10.2147/OTT.S169957

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

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

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