Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Mugar Building, 360 Huntington Avenue, Boston, Massachusetts 02115, USA.
Pharm Res. 2011 Feb;28(2):301-8. doi: 10.1007/s11095-010-0242-3. Epub 2010 Aug 21.
To evaluate the potential of palmitoyl ascorbate (PA)-loaded micelles for ascorbate-mediated cancer cell targeting and cytotoxicity.
PA was incorporated in polyethylene glycol-phosphatidyl ethanolamine micelles at varying concentrations. The formulations were evaluated for PA content by RP-HPLC. A stable formulation was selected based on size and zeta potential measurements. A co-culture of cancer cells and GFP-expressing non-cancer cells was used to determine the specificity of PA micelle binding. In vitro cytotoxicity of the micellar formulations towards various cancer cell lines was investigated using a cell viability assay. To elucidate the mechanism of action of cell death in vitro, the effect of various H(2)O(2) scavengers and metal chelators on PA-mediated cytotoxicity was studied. The in vivo anti-cancer activity of PA micelles was studied in female Balb/c mice bearing a murine mammary carcinoma (4T1 cells).
PA micelles associated preferentially with various cancer cells compared to non-cancer cells in co-culture. PA micelles exhibited anti-cancer activity in cancer cell lines both in vitro and in vivo. The mechanism of cell death was due primarily to generation of reactive oxygen species (ROS).
The anti-cancer activity of PA micelles associated with its enhanced cancer cell binding and subsequent generation of ROS.
评估棕榈酰抗坏血酸（PA）负载胶束用于抗坏血酸介导的癌细胞靶向和细胞毒性的潜力。
将 PA 以不同浓度掺入聚乙二醇-磷脂酰乙醇胺胶束中。通过反相高效液相色谱法（RP-HPLC）评估制剂中的 PA 含量。根据粒径和 zeta 电位测量结果选择稳定的制剂。使用共培养的癌细胞和 GFP 表达的非癌细胞来确定 PA 胶束结合的特异性。使用细胞活力测定法研究胶束制剂对各种癌细胞系的体外细胞毒性。为了阐明体外细胞死亡的作用机制，研究了各种 H（2）O（2）清除剂和金属螯合剂对 PA 介导的细胞毒性的影响。在携带鼠乳腺癌（4T1 细胞）的雌性 Balb/c 小鼠中研究了 PA 胶束的体内抗癌活性。
PA 胶束与共培养中的各种癌细胞相比，优先与非癌细胞结合。PA 胶束在体外和体内的癌细胞系中均表现出抗癌活性。细胞死亡的机制主要是由于活性氧（ROS）的产生。
PA 胶束的抗癌活性与其增强的癌细胞结合以及随后产生的 ROS 有关。
