Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Biomaterials Group, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India.
Biomaterials. 2014 Feb;35(5):1643-56. doi: 10.1016/j.biomaterials.2013.10.074. Epub 2013 Nov 14.
Curcumin, because of its distinguishing ability to inhibit activation of transcription factor linked to chemoresistance and drug transporters, is now being co-administered with various potent anti-cancer drugs. In the present study, we report on such potentiating capabilities of curcumin in anti-angiogenic cancer therapy. With a view to simultaneously deliver curcumin and doxorubicin to tumor vasculature in anti-angiogenic cancer therapy, herein we report on the design & synthesis of a tumor vasculature targeting pegylated RGDK-lipopeptide. We show that curcumin & doxorubicin co-encapsulated within the liposomes of the presently described pegylated RGDK-lipopeptide exhibit synergism in inhibiting proliferation, invasion and migration of both tumor and endothelial cells presumably by inhibiting proliferation and metastasis related genes both at mRNA & protein levels. Pronounced tumor growth inhibition was observed in mice treated with formulations containing both the drugs. Tumor growth inhibition was found to be 2-3 folds less in mice treated with formulations containing only curcumin or only doxorubicin. The presently described liposomal system is expected to find future use for simultaneously delivering potentially any combinations of hydrophilic and hydrophobic potent small molecule cancer therapeutics to tumor vasculature in anti-angiogenic cancer therapy.
姜黄素由于其独特的抑制与化学抗性和药物转运体相关的转录因子激活的能力，现在正与各种有效的抗癌药物联合使用。在本研究中，我们报告了姜黄素在抗血管生成癌症治疗中的这种增效作用。为了在抗血管生成癌症治疗中同时将姜黄素和阿霉素递送到肿瘤血管中，我们设计并合成了一种靶向肿瘤血管的聚乙二醇化 RGDK-脂质肽。我们表明，姜黄素和阿霉素共同包封在目前描述的聚乙二醇化 RGDK-脂质肽的脂质体中，通过在 mRNA 和蛋白水平上抑制增殖和转移相关基因，在抑制肿瘤和内皮细胞的增殖、侵袭和迁移方面表现出协同作用。用含有两种药物的制剂处理的小鼠观察到明显的肿瘤生长抑制。用仅含有姜黄素或仅含有阿霉素的制剂处理的小鼠，肿瘤生长抑制作用降低了 2-3 倍。目前描述的脂质体系统有望在未来用于同时向抗血管生成癌症治疗中的肿瘤血管递送电镜下可见的任何组合的亲水性和疏水性有效的小分子癌症治疗药物。
