Targeted Nanocarriers for Treatment of Lung Cancer

描述(申请人提供)：肺癌是美国男性和女性癌症死亡的主要原因。采用传统方法治疗的肺癌患者的存活率仍远远不能令人满意。最近，利用新型药物治疗肺癌的新方法已经产生，这些药物选择性地抑制肿瘤血液供应，从而结合传统的抗癌或抗血管生成药物来控制癌细胞的存活、增殖和/或转移 临床兴趣。我们的初步研究表明，dIM-C-pPhC6H5(dim-P)，a，c取代 二吲哚甲烷具有抗血管生成活性。本研究的目的是制备聚乙二醇化CREKA多肽包裹的Dim-P纳米载体(PCNCs-D)，并研究其抗肿瘤活性和抗血管生成作用。我们的初步试管形成实验、免疫印迹和免疫组织化学研究强烈表明DIM-P和PCNC-D具有抗血管生成活性。我们的假设是：靶向聚乙二醇化的纳米载体dim-P将靶向肿瘤血管，增加血浆半衰期，从而通过对肺癌发挥抗血管生成活性来抑制肿瘤生长。这项建议的新方面是研究一种使用PCNC-D的新型靶向纳米载体药物输送治疗方法的抗血管生成效果，并了解体内肿瘤模型中参与抗血管生成作用的分子途径。拟议研究的假设和目标应遵循以下特定目标：(1)构建DIM-P的靶向纳米载体；(2)评估DIM-P的靶向纳米载体的抗血管生成和体内疗效；以及(3)阐明在退行性肿瘤中参与PCNC-D活性的机制。这些研究的结果将证明 新型PCNC-D作为抗血管生成药物有效靶向给药的研究 用于肺癌治疗。拟议的研究具有很强的潜力来证明 未经测试的高度创新的肺癌治疗方法。

DESCRIPTION (provided by applicant): Lung cancer is the leading cause of cancer death in both men and women in the United States. Survival rate of lung cancer patients treated by conventional modalities remains far from satisfactory. Recently, new approaches in the treatment of lung cancer with novel drugs that selectively inhibit tumor blood supply thus controlling cancer cell survival, proliferation and/or metastasis in combination with conventional anticancer or antiangiogenic drugs have generated clinical interest. Our preliminary studies demonstrated that DIM-C-pPhC6H5 (DIM-P), a c substituted diindolylmethanes exhibits antiangiogenic activity. The objective of this proposal is to formulate targeted pegylated CREKA peptide coated nanocarriers of DIM-P (PCNCs-D) and investigate its antitumor activity and antiangiogenic potential for treatment of lung cancer. Our preliminary tube formation assay, western blot and immunohistochemistry studies strongly suggest that DIM-P and PCNCs-D exhibits antiangiogenic activity. Our hypothesis is: targeted pegylated nanocarriers of DIM-P will target tumor blood vasculature and increase plasma half life thereby inhibiting tumor growth by exerting antiangiogenic activity against lung tumors. The novel aspects of this proposal are to study the antiangiogenic efficacy of a novel targeted nanocarrier drug delivery therapy approach using PCNCs-D and to understand the molecular pathways involved in the antiangiogenic effect in an in vivo tumor model. The hypotheses and objectives of the proposed research shall be pursued with the following specific aims: (1) To formulate targeted nanocarriers of DIM-P; (2) To evaluate antiangiogenic and in vivo efficacy of targeted nanocarriers of DIM-P; and (3) To elucidate mechanism pathways involved in PCNCs-D activity in regressed tumors. The results emanating from these studies will demonstrate the usefulness of novel PCNCs-D as an effective targeted delivery of antiangiogenic drug for lung cancer treatment. The proposed studies have strong potential to demonstrate an untested and highly innovative approach for lung cancer treatment.