Nano Approaches to Modulate Host Cell Response for Cancer Therapy

 描述（由申请人提供）：靶向免疫和基质组分的宿主反应代表了通过身体内置防御机制克服癌症的改变游戏规则的机会。我们在这一应用中的重点是通过纳米方法利用宿主反应进行癌症疾病管理和治疗。我们建议开发针对黑色素瘤和非小细胞肺癌（NSCLC）的生物制剂和免疫调节剂和化疗的靶向方法，利用在UNC-Chapel Hill开发的创新纳米技术。我们在这份建议书中提出了四个项目。这些项目围绕的中心主题是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有效和更有效地递送siRNA，这是药物递送的关键挑战。该项目针对Vemurafenib耐药性黑色素瘤，并强调直接抑制耐药性，与新的疫苗方法相结合。项目2评估了通过非润湿模板中的颗粒复制（PRINT（r））纳米颗粒通过新颖的抗原递送来增强抗肿瘤免疫应答的方法。独特的佐剂，如病原体相关的分子模式，正在探索，以及在黑色素瘤的宿主免疫阻断剂的主动抑制。项目3利用抗原释放的生物学和辐射后的远位效应，通过专门设计的纳米颗粒增强抗原捕获和对黑色素瘤原发肿瘤和转移瘤的免疫反应。项目4使用具有高容量负载的聚合物胶束来递送靶向肿瘤微环境以及NSCLC中的肿瘤细胞的治疗剂。总之，我们的卡罗莱纳CCNE专注于改善癌症疾病的控制和管理，通过以创新方式使用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远远超出正在研究的特定疾病状况。

 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.