Nanoparticle Co-delivery of RNAi and Chemotherapy for Multidrug Resistant Cancers

纳米粒子联合递送 RNAi 和化疗治疗多重耐药癌症

• 批准号: 8689250
• 负责人: Jinjun Shi
• 金额: $ 23.41万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8689250
• 关键词: ABCB1 gene; Address; Adverse effects; Antineoplastic Agents; BCL2 gene; Cells; Cessation of life; Characteristics; Charge; Chemotherapy-Oncologic Procedure; Clinical; Combined Modality Therapy; Development; Disease; Drug Combinations; Drug Delivery Systems; Drug resistance; Emulsions; Engineering; Evaluation; Gene Silencing; Generations; Hybrids; In Vitro; Individual; Kinetics; Lead; Libraries; Ligands; Lipids; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of prostate; Mediating; MicroRNAs; Molecular; Multi-Drug Resistance; Nanotechnology; Outcome; P-Glycoprotein; Pharmaceutical Preparations; Phase; Physiological; Polymers; Property; Proteins; RNA Interference; RPS6KA5 gene; Research; Resistance; Small Interfering RNA; Surface; System; Taxane Compound; Technology; Testing; Therapeutic; Therapeutic Index; Transferrin; Xenograft Model; aptamer; base; biocompatible polymer; biodegradable polymer; cancer cell; chemotherapeutic agent; chemotherapy; combination cancer therapy; controlled release; cytotoxic; density; design; improved; in vivo; interest; nanomedicine; nanoparticle; nanoparticulate; nanoscale; nanosystems; nanotherapeutic; particle; prostate cancer cell; receptor; self assembly; spatiotemporal; stem; targeted delivery; taxane; uptake

ABSTRACT A critical barrier to effective cancer chemotherapy is the development of multidrug resistance (MDR) in cancer cells. The broad and long-term objective of this project is to develop advanced nanomedicinal approaches for the treatment of multidrug resistant cancers. We believe that nanomedicinal therapy, which can simultaneously deliver RNAi therapeutics to suppress MDR and chemotherapeutic agents to induce the death of cancer cells, will be of particular interest in addressing the challenge of MDR in cancer chemotherapy. Specifically, we will design and develop nanoparticulate platforms for the effective co-delivery of RNAi and anti-cancer agents with a synergistic drug ratio to taxane-resistant lung and prostate cancer cells, by using biodegradable and biocompatible polymers and lipids. The contribution of different drug-resistant proteins to cancer MDR will be compared. The physicochemical properties of the nanoparticles will also be optimized to overcome the physiological barriers in vivo, while keeping the co-delivery of RNAi and chemotherapy safe and effective. Furthermore, in the R00 independent phase, the nanoparticulate platform will be precisely engineered to control the temporal release of individual agents and to achieve targeted drug delivery. We hypothesize that the spatiotemporal controlled delivery of nanotherapeutics can maximize the desired effects of RNAi and anti-cancer agents for multidrug resistant cancers, while minimizing their toxic side effects. If successful, this project will lay the groundwork for wider applications of the nanotechnology-based targeted combination therapy for cancer and other diseases.

抽象的 有效癌症化学疗法的关键障碍是多药耐药性的发展 （MDR）在癌细胞中。该项目的广泛和长期目标是发展高级 纳米医学方法用于治疗多药耐药性癌症。我们相信 纳米医学疗法，可以同时提供RNAi疗法以抑制MDR和 化学治疗剂诱导癌细胞死亡，在 解决MDR在癌症化疗中的挑战。具体来说，我们将设计和开发 与A的有效共同传递和抗癌剂的纳米式平台 通过使用可生物降解和 生物相容性聚合物和脂质。不同药物蛋白对癌症的贡献 将比较MDR。纳米颗粒的物理化学特性也将优化为 克服体内的生理障碍，同时保持RNAi和化学疗法的共同分娩 安全有效。此外，在R00独立阶段，纳米刻度平台将是 精确设计以控制单个代理的时间释放并实现目标药物 送货。我们假设纳米疗法的时空控制输送可以 最大化RNAi和抗癌药对多药耐药性癌症的期望作用，而 最小化其毒性副作用。如果成功，该项目将为更广泛的基础奠定基础 基于纳米技术的癌症和其他基于纳米技术的靶向组合疗法的应用 疾病。