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Targeted Nanocarriers for Treatment of Lung Cancer

用于治疗肺癌的靶向纳米载体

基本信息

批准号：
8018928
负责人：
Mandip Singh Sachdeva
金额：
$ 28.03万
依托单位：
FLORIDA AGRICULTURAL AND MECHANICAL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8018928
关键词：
A549 Accounting Adverse reactions Affinity Agonist Angiogenesis Inhibitors Anti-Inflammatory Agents Anti-inflammatory Antineoplastic Agents Apoptotic Behavior Binding Biological Assay Biological Availability Blood Cancer Etiology Cancer Patient Cell Survival Cells Cessation of life Clinical Coagulation Process Data Drug Delivery Systems Drug Formulations Drug Kinetics Exhibits Goals Growth Half-Life Homing Immunohistochemistry In Vitro Investigation Laboratories Lead Legal patent Link Lipids Lung Neoplasms Malignant Neoplasms Malignant neoplasm of lung Modality Modeling Molecular Mus Neoplasm Metastasis Non-Small-Cell Lung Carcinoma Normal Cell Nude Mice Oral Outcome PECAM1 gene PPAR gamma Pathway interactions Peptides Peroxisome Proliferator-Activated Receptors Pharmaceutical Preparations Phase I Clinical Trials Plasma Plasma Proteins Positioning Attribute Proteins Research Role Solubility Survival Rate System Techniques Testing Time Toxic effect Tube Tumor Cell Line United States Vascular Endothelial Growth Factors Western Blotting Woman angiogenesis anticancer activity arginylglutamate base cancer cell cancer therapy chemotherapy density diindolylmethane docetaxel effective therapy in vivo innovation interest matrigel men nanocarrier nanoparticle nanostructured neoplastic cell novel novel strategies particle targeted delivery tumor tumor growth tumor vascular supply

项目摘要

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. PUBLIC HEALTH RELEVANCE: The objective of this proposal is to formulate targeted pegylated CREKA peptide coated nanocarriers of DIMC-pPhC6H5 (DIM-P) and investigate its antitumor activity and antiangiogenic pathways for treatment of lung cancer. The research proposed in this application is significant because it is expected to provide new data that will lead to significant anticancer activity and decreased adverse reactions than encountered in using multiple chemotherapeutic drugs in lung cancer patients.

描述（由申请人提供）：肺癌是美国男性和女性癌症死亡的主要原因。传统方式治疗的肺癌患者生存率仍远不能令人满意。近年来，与传统抗癌或抗血管生成药物联合使用选择性抑制肿瘤血液供应从而控制癌细胞存活、增殖和/或转移的新型药物治疗肺癌的新途径已经出现