Li Jun, Xu Wenqing, Yuan Xiaoli, Chen Huaiwen, Song Hao, Wang Bingquan, Han Jun
College of Pharmacy, Liaocheng University, Liaocheng, Shandong.
Railway Police College, Zhengzhou.
Int J Nanomedicine. 2017 Sep 18;12:6909-6921. doi: 10.2147/IJN.S144184. eCollection 2017.
Breast cancer stem cells (CSCs) are responsible for the initiation, recurrence, and metastasis of breast cancer. Sufficient evidence has established that breast cancer cells can spontaneously turn into breast CSCs. Thus, it is essential to simultaneously target breast CSCs and cancer cells to maximize the efficacy of breast cancer therapy. HER2 has been found to be overexpressed in both breast CSCs and cancer cells. We developed salinomycin-loaded polymer-lipid hybrid anti-HER2 nanoparticles (Sali-NP-HER2) to target both HER2-positive breast CSCs and cancer cells.
The antitumor activity of Sali-NP-HER2 constructed by conjugating anti-HER2 antibodies to polymer-lipid salinomycin nanoparticles was evaluated in vitro and in vivo.
Sali-NP-HER2 efficiently bound to HER2-positive breast CSCs and cancer cells, resulting in enhanced cytotoxic effects compared with non-targeted nanoparticles or salinomycin. In mice bearing breast cancer xenografts, administration of Sali-NP-HER2 exhibited superior efficacy in inhibiting tumor growth. Sali-NP-HER2 reduced the breast tumorsphere formation rate and the proportion of breast CSCs more effectively than non-targeted nanoparticles or salinomycin alone.
Sali-NP-HER2 represents a promising approach in treating HER2-positive breast cancer by targeting both breast CSCs and cancer cells.
乳腺癌干细胞（CSCs）是乳腺癌发生、复发和转移的根源。已有充分证据表明乳腺癌细胞可自发转变为乳腺癌干细胞。因此，同时靶向乳腺癌干细胞和癌细胞对于最大化乳腺癌治疗效果至关重要。研究发现HER2在乳腺癌干细胞和癌细胞中均有过表达。我们研发了负载沙利霉素的聚合物 - 脂质杂化抗HER2纳米颗粒（Sali - NP - HER2），以同时靶向HER2阳性的乳腺癌干细胞和癌细胞。
通过将抗HER2抗体与聚合物 - 脂质沙利霉素纳米颗粒偶联构建的Sali - NP - HER2的抗肿瘤活性在体外和体内进行了评估。
Sali - NP - HER2能有效结合HER2阳性的乳腺癌干细胞和癌细胞，与非靶向纳米颗粒或沙利霉素相比，其细胞毒性作用增强。在携带乳腺癌异种移植瘤的小鼠中，给予Sali - NP - HER2在抑制肿瘤生长方面表现出更高的疗效。Sali - NP - HER2比非靶向纳米颗粒或单独的沙利霉素更有效地降低了乳腺肿瘤球形成率和乳腺癌干细胞的比例。
Sali - NP - HER2通过同时靶向乳腺癌干细胞和癌细胞，为治疗HER2阳性乳腺癌提供了一种有前景的方法。
