Nano Approaches to Modulate Host Cell Response for Cancer Therapy

调节宿主细胞反应以进行癌症治疗的纳米方法

• 批准号: 8960618
• 负责人: Leaf Huang
• 金额: $ 226.19万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8960618
• 关键词: Address; Adjuvant; Affect; Animal Model; Antigen Presentation; Antigens; Basic Science; Biology; CCNE1 gene; Cancer Etiology; Cancer Patient; Cells; Cessation of life; Clinical; Coupled; Defense Mechanisms; Development; Disease; Disease Management; Drug Delivery Systems; Drug resistance; Funding; Immune; Immune response; Immunity; Immunologic Adjuvants; Immunologics; Immunology; Immunosuppression; Immunotherapy; Malignant Neoplasms; Malignant neoplasm of lung; Melanoma Cell; Messenger RNA; Methods; Micelles; Molecular; Nanotechnology; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Patients; Pattern; Pharmaceutical Preparations; Primary Neoplasm; Radiation Oncology; Research; Resistance; Small Interfering RNA; Somatotype; Therapeutic; Translations; Work; angiogenesis; anticancer research; cancer cell; cancer therapy; chemotherapy; design; disorder control; experience; improved; inhibitor/antagonist; innovation; interest; irradiation; melanoma; nano; nanoparticle; neoplastic cell; novel; novel vaccines; particle; pathogen; public health relevance; response; success; therapeutic target; tumor; tumor microenvironment

 DESCRIPTION (provided by applicant): Host response targeting of both immune and stromal components, represents a game changing opportunity to overcome cancer through the body's built in defense mechanisms. Our focus in this application is to exploit the host response through nano approaches for cancer disease management and treatment. We propose developing targeted methods for the delivery of biologics and, immunologic- modifiers and chemotherapies against melanoma and non-small cell lung cancers (NSCLC), utilizing innovative nanotechnologies developed here at UNC-Chapel Hill. We have proposed four projects in this proposal. The projects revolve around the central theme of exploiting the host response against tumors with an emphasis on the immune response. Project 1 is the designated basic science project since novel polymetformin nanoparticles are being proposed for more efficient and effective delivery of siRNA, which is a critical challenge for drug delivery The project targets Vemurafenib resistant melanoma, and emphasizes direct suppression of drug resistance that is coupled with a new vaccine approach. Project 2 evaluates ways to enhance the anti-tumor immune response through novel delivery of antigens via Particle Replication in Non-wetting Templates (PRINT(r)) nanoparticles. Unique adjuvants, such as Pathogen-associated Molecular Patterns, are being explored as well as the active suppression of blockers of host immunity in melanoma. Project 3 takes advantage of the biology of antigen release and the abscopal effect post irradiation through specifically designed nanoparticles to enhance antigen capture and the immune response to both primary tumors and metastases in melanoma. Project 4 uses polymeric micelles with high capacity loading to deliver therapeutics targeted to the tumor microenvironment as well as tumor cells in NSCLC. In summary, our Carolina CCNE is focused on improving cancer disease control and management to enhance treatment options for patients by the use of novel nanoparticles used in innovative ways that should have impact far beyond the specific disease conditions that are being studied.

 描述(由申请人提供)：免疫和基质成分的宿主反应靶向，代表着通过身体内置的防御机制战胜癌症的一个改变游戏规则的机会。我们在这项应用中的重点是通过纳米方法利用宿主的反应来管理和治疗癌症。我们建议开发有针对性的方法，利用北卡罗来纳大学教堂山分校开发的创新纳米技术，提供针对黑色素瘤和非小细胞肺癌(NSCLC)的生物制剂、免疫调节剂和化疗药物。在这份提案中，我们提出了四个项目。这些项目围绕着一个中心主题，即利用宿主对肿瘤的反应，重点是免疫反应。项目1是指定的基础科学项目，因为新的聚二甲双胍纳米颗粒被提出用于更高效和有效地传递siRNA，这是药物传递的关键挑战。该项目针对Vemurafenib耐药黑色素瘤，强调直接抑制耐药性，并结合新的疫苗方法。项目2评估了通过在非润湿模板(Print(R))纳米颗粒中进行粒子复制来新型抗原传递来增强抗肿瘤免疫反应的方法。人们正在探索独特的佐剂，如病原体相关的分子模式，以及在黑色素瘤中主动抑制宿主免疫阻滞剂。项目3利用辐射后抗原释放的生物学和非局域效应，通过专门设计的纳米颗粒来增强抗原捕获和对黑色素瘤原发肿瘤和转移的免疫反应。项目4使用高容量负载的聚合物胶束来输送针对非小细胞肺癌肿瘤微环境和肿瘤细胞的治疗药物。总而言之，我们卡罗莱纳州的CCNE专注于改善癌症疾病的控制和管理，通过使用以创新方式使用的新型纳米颗粒来增强患者的治疗选择，这些纳米颗粒的影响应该远远超出正在研究的特定疾病条件。