Song Hao, Su Xiao, Yang Kaixuan, Niu Fangfang, Li Jun, Song Jinjing, Chen Huaiwen, Li Bohua, Li Wei, Qian Weizhu, Cao Xuesong, Guo Shangjing, Dai Jianxin, Feng Si-Shen, Guo Yajun, Yin Chuan, Gao Jie
J Biomed Nanotechnol. 2015 Nov;11(11):1927-46. doi: 10.1166/jbn.2015.2129.
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.
癌症起始细胞（CIC）是具有与正常干细胞相似特性的致瘤癌细胞。CD20是黑色素瘤CIC的一种表型，它导致黑色素瘤耐药。长春新碱（VCR）常用于黑色素瘤治疗；然而，已发现它对CIC无效。为了靶向CD20 +黑色素瘤CIC，我们制备了与CD20抗体偶联的含VCR免疫脂质体（VCR-Lip-CD20）。优化了免疫脂质体的药物释放曲线和抗体介导的靶向作用，以靶向CD20 +黑色素瘤CIC。该免疫脂质体具有理想的粒径（163 nm）、药物包封效率（91.8%）和药物释放曲线。我们证明，即使CHO-CD20细胞仅占CHO-CD20和CHO细胞混合群体的0.1%，这些免疫脂质体仍能成功靶向超过55%的CD20 +中国仓鼠卵巢细胞（CHO-CD20）。用VCR-Lip-CD20、VCR脂质体（VCR-Lip）和VCR处理WM266-4黑色素瘤乳腺球96小时后，发现递送药物的ICo值分别为53.42、98.99和99.09 μg/mL，这表明VCR-Lip-CD20的效果比VCR-Lip和VCR高1.85倍。VCR-Lip-CD20几乎可以完全消除WM266-4乳腺球在体内的致瘤能力，并在WM266-4黑色素瘤异种移植小鼠中显示出最佳治疗效果。值得注意的是，VCR-Lip-CD20在体外和体内均可选择性杀死WM266-4细胞群体中的CD20 +黑色素瘤CIC。我们证明VCR-Lip-CD20有潜力有效靶向并杀死CD20 +黑色素瘤CIC。
