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）：针对免疫和基质成分的宿主反应代表了通过人体内置防御机制克服癌症的改变游戏规则的机会我们在本申请中的重点是通过纳米方法利用宿主反应来治疗癌症疾病。我们建议利用此处开发的创新纳米技术，开发针对黑色素瘤和非小细胞肺癌 (NSCLC) 的生物制剂、免疫调节剂和化疗的靶向方法。北卡罗来纳大学教堂山分校在该提案中提出了四个项目，其中心主题是利用宿主对肿瘤的反应，重点是免疫反应，因为新型聚二甲双胍纳米颗粒正在研发中。提议更高效和有效地递送 siRNA，这是药物递送的一个关键挑战。该项目针对 Vemurafenib 耐药性黑色素瘤，并强调直接抑制耐药性，并与新的疫苗方法相结合，项目 2 评估了增强的方法。正在探索通过非润湿模板中的粒子复制（PRINT（r））纳米粒子新颖地递送抗原来产生抗肿瘤免疫反应，以及对病原体相关分子模式等独特佐剂的主动抑制。黑色素瘤的宿主免疫通过专门设计的纳米粒子，利用抗原释放的生物学特性和放射后的远隔效应来增强抗原捕获和对两种原发性肿瘤的免疫反应。项目 4 使用高容量负载的聚合物胶束来提供针对肿瘤微环境以及 NSCLC 肿瘤细胞的治疗药物。 总之，我们的 Carolina CCNE 致力于改善癌症疾病控制和管理，以增强癌症的治疗选择。以创新方式使用新型纳米颗粒的患者，其影响应远远超出正在研究的特定疾病状况。