Biodegradable Polymeric Nanosphere Drug Delivery System For Cancer Chemotherapy

用于癌症化疗的可生物降解聚合物纳米球药物输送系统

• 批准号: 7341850
• 负责人: EMMANUEL O AKALA
• 金额: $ 14.8万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7341850
• 关键词: 2-hydroxyethyl methacrylate; Affect; American; Antineoplastic Agents; Belief; Biocompatible; Biological; Biological Assay; Biological Markers; Breast; Breast Carcinoma; Cancer Detection; Cardiovascular Diseases; Cell Death; Cell Line; Cell Survival; Cells; Chemicals; Chemotherapy-Oncologic Procedure; Clinic; Colorectal Cancer; Condition; Crosslinker; Development; Dose; Drug Carriers; Drug Combinations; Drug Controls; Drug Delivery Systems; Drug Efflux; Drug resistance; Endocytosis; Ethylene Glycols; Evaluation; Future; Gender; Glass; Goals; Health; Heterogeneity; Hormones; Human; Hydrolysis; Image; Immune; In Vitro; Infection; Inherited; Intrinsic factor; Ionizing radiation; Life; Ligands; Lung; Malignant Epithelial Cell; Malignant Neoplasms; Measurement; Metabolism; Molecular Weight; Morphology; Mutation; Nanosphere; Paclitaxel; Particle Size; Patients; Pharmaceutical Preparations; Property; Prostate; Pump; Radiation; Reporting; Research; Research Project Grants; Resistance; Scanning Electron Microscopy; Screening for cancer; Site; Solutions; Spectroscopy, Fourier Transform Infrared; Surface; System; Temperature; Time; Tobacco smoking; Transmission Electron Microscopy; Tumor Burden; Ultraviolet Rays; United States; United States Food and Drug Administration; Virus Diseases; Water; base; cancer cell; cancer diagnosis; cancer therapy; carcinogenesis; cell growth; controlled release; copolymer; crosslink; cytotoxicity; design; efflux pump; ethylene glycol; in vivo; killings; melting; mortality; nanoparticle; neoplastic cell; poly(L-lactide); poly(lactic acid); poly(lactide); receptor mediated endocytosis; targeted delivery; trafficking; uptake

DESCRIPTION (provided by applicant): The importance of the problem of cancer is shown by the report which indicates that more than 1.3 million cases of cancer are diagnosed annually and that cancer claims an estimated 570,280 lives in the United States each year. It is believed that cancer is second only to cardiovascular diseases as a cause of mortality among Americans. The most common cancers in United States are prostate, breast, lung and colorectal cancers. Thus cancer does not discriminate on the basis of gender. Both extrinsic factors [e.g., tobacco smoking, chemicals, drugs, hormones, radiations (such as ionizing radiations and ultraviolet light), and infections (such as viral infections)] and patient intrinsic factors (e.g., inherited metabolism mutations, hormones, and immune conditions) are believed to be important initiators of cancers. Frantic efforts have been made over the years to identify factors affecting successful treatment of cancer: tumor burden, tumor-cell heterogeneity, drug resistance, dose intensity, and poor selectivity of the drug. Moreover, a great deal of research has been carried out to find ways and means to circumvent the problems of cancer treatment: targeted delivery of drugs to cancer, in vivo detection of cancer biomarkers, detection of cancer biomarkers ex vivo, overcoming biological barriers to the biophase (site of action), identification of potential targets and targeting moieties for anti-cancer drug delivery systems, drug combination, and the development of efficient drug carriers. There is a need for the integration of all these efforts. The development of multifunctional polymeric nanospheres for cancer therapy, which is the long-term objective of this application, could make the integration possible. The core of the nanosphere can be loaded with anti-cancer agents, imaging agent, and agents to overcome pump and non-pump resistance; targeting moieties and agents responsive to biomarkers could be tagged to the external coating made of poly(ethylene glycol). All these will achieve early detection of cancer and provide effective killing of the cancer cells. The goal of the research in this application is to initiate efforts that will make it possible to achieve the capabilities of multifunctional nanoparticles by developing paclitaxel-loaded stealth nanospheres based on biocompatible and biodegradable poly(lactic acid). Synthesis of biodegradable and biocompatible macromonomers, fabrication and characterization of paclitaxel-loaded nanopsheres and their evaluation for cell uptake and cytotoxicity in the BT-20 human breast carcinoma cell line are the focus of this proposal.

描述(由申请人提供)：报告表明了癌症问题的重要性，该报告指出，美国每年有超过130万例癌症被诊断出来，估计每年有570,280人死于癌症。据认为，在美国人中，癌症是仅次于心血管疾病的第二大死亡原因。美国最常见的癌症是前列腺癌、乳腺癌、肺癌和结直肠癌。因此，癌症不存在性别歧视。外界因素[如吸烟、化学物质、药物、激素、辐射(如电离辐射和紫外线)、感染(如病毒感染)]和患者内在因素(如遗传代谢突变、激素和免疫状况)都被认为是癌症的重要诱因。 多年来，人们一直在努力确定影响癌症成功治疗的因素：肿瘤负担、肿瘤细胞异质性、耐药性、剂量强度和药物的低选择性。此外，为了寻找规避癌症治疗问题的方法和手段，人们进行了大量的研究：靶向给药到癌症，体内癌症生物标志物的检测，体外癌症生物标志物的检测，克服生物相(作用部位)的生物障碍，识别潜在的靶点和抗癌药物输送系统的靶向部分，药物组合，以及高效药物载体的开发。有必要整合所有这些努力。用于癌症治疗的多功能聚合物纳米球的开发，这是这一应用的长期目标，可以使集成成为可能。纳米球的核心可以负载抗癌剂、显像剂和克服泵和非泵阻力的试剂；靶向部分和对生物标记物有反应的试剂可以标记到聚乙二醇制的外部涂层上。所有这些都将实现癌症的早期发现，并提供有效的癌细胞杀灭。这项应用研究的目标是通过开发基于生物相容和可生物降解的聚乳酸的紫杉醇隐形纳米球来实现多功能纳米粒子的能力。可生物降解和生物相容的大分子单体的合成、紫杉醇纳米微粒的制备和表征以及它们对BT-20人乳腺癌细胞系的细胞摄取和细胞毒性的评价是本提案的重点。