title: CD20 Antibody-Conjugated Immunoliposomes for Targeted Chemotherapy of Melanoma Cancer Initiating Cells.
abstract: Cancer initiating cells (CIC) are tumorigenic cancer cells that have properties similar to normal stem cells. CD20 is a phenotype of melanoma CIC that is responsible for melanoma drug resistance. Vincristine (VCR) is commonly used in melanoma therapy; however, it has been found ineffective against CIC. To target CD20+ melanoma CIC, we prepared VCR-containing immunoliposomes that were conjugated to CD20 antibodies (VCR-Lip-CD20). The drug release profile and the antibody-mediated targeting of the immunoliposomes were optimized to target CD20+ melanoma CIC. The immunoliposomes had desirable particle size (163 nm), drug encapsulation efficiency (91.8%), and drug release profile. We demonstrated that these immunoliposomes could successfully target more than 55% of CD20+ Chinese Hamster Ovary cells (CHO-CD20) even when the CHO-CD20 cells accounted for only 0.1% of a mixed population of CHO-CD20 and CHO cells. After treating WM266-4 melanoma mammospheres for 96 h, the ICo values of the drug delivered in VCR-Lip-CD20, VCR-Lip (VCR liposomes), and VCR were found to be 53.42, 98.99, and 99.09 μg/mL, respectively, suggesting that VCR-Lip-CD20 was 1.85 times more effective than VCR-Lip and VCR. VCR-Lip-CD20 could almost completely remove the tumorigenic ability of WM266-4 mammospheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. Significantly, VCR-Lip-CD20 could selectively kill CD20+ melanoma CIC in populations of WM266-4 cells both in vitro and in vivo. We demonstrated that VCR-Lip-CD20 has the potential to efficiently target and kill CD20+ melanoma CIC.
authors.forename: Hao
authors.initials: H
authors.lastname: Song
authors.forename: Xiao
authors.initials: X
authors.lastname: Su
authors.forename: Kaixuan
authors.initials: K
authors.lastname: Yang
authors.forename: Fangfang
authors.initials: F
authors.lastname: Niu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Jinjing
authors.initials: J
authors.lastname: Song
authors.forename: Huaiwen
authors.initials: H
authors.lastname: Chen
authors.forename: Bohua
authors.initials: B
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Weizhu
authors.initials: W
authors.lastname: Qian
authors.forename: Xuesong
authors.initials: X
authors.lastname: Cao
authors.forename: Shangjing
authors.initials: S
authors.lastname: Guo
authors.forename: Jianxin
authors.initials: J
authors.lastname: Dai
authors.forename: Si-Shen
authors.initials: SS
authors.lastname: Feng
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
authors.forename: Chuan
authors.initials: C
authors.lastname: Yin
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D016466:CHO Cells; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D023041:Xenograft Model Antitumor Assays
chemical_list: D018951:Antigens, CD20; D000970:Antineoplastic Agents; D008081:Liposomes