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）： 报告显示了癌症问题的重要性，该报告指出，每年诊断出超过 130 万例癌症，在美国，癌症每年夺去约 570,280 人的生命。据信，癌症是美国人死亡的第二大原因，仅次于心血管疾病。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。外在因素[例如吸烟、化学品、药物、激素、辐射（例如电离辐射和紫外线）和感染（例如病毒感染）]和患者内在因素（例如遗传代谢突变、激素和免疫）条件）被认为是癌症的重要引发因素。 多年来，人们一直在努力找出影响癌症成功治疗的因素：肿瘤负荷、肿瘤细胞异质性、耐药性、剂量强度和药物选择性差。此外，人们还进行了大量的研究来寻找规避癌症治疗问题的方法和手段：对癌症进行靶向递送药物、体内检测癌症生物标志物、离体检测癌症生物标志物、克服癌症治疗的生物障碍。生物相（作用位点）、抗癌药物输送系统的潜在靶点和靶向部分的识别、药物组合以及高效药物载体的开发。需要整合所有这些努力。开发用于癌症治疗的多功能聚合物纳米球是该应用的长期目标，可以使整合成为可能。纳米球核心可负载抗癌剂、显像剂、克服泵阻力和非泵阻力的药剂；对生物标志物有反应的靶向部分和试剂可以被标记到由聚乙二醇制成的外部涂层上。所有这些都将实现癌症的早期发现并有效杀死癌细胞。本申请研究的目标是通过开发基于生物相容性和可生物降解的聚乳酸的负载紫杉醇的隐形纳米球来实现多功能纳米颗粒的功能。可生物降解和生物相容性大分子单体的合成、负载紫杉醇的纳米球的制造和表征以及它们在 BT-20 人乳腺癌细胞系中的细胞摄取和细胞毒性的评估是本提案的重点。