Nanocrystals for the Treatment of Multidrug Resistance in Cancer

用于治疗癌症多药耐药性的纳米晶体

• 批准号: 8038042
• 负责人: FENG LIU
• 金额: $ 30.71万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-17 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8038042
• 关键词: Address; Affect; Albumin-Stabilized Nanoparticle Paclitaxel; Antineoplastic Agents; Artificial nanoparticles; Behavior; Biodistribution; Blood; Blood Circulation; Cell Line; Cells; Characteristics; Chemotherapy-Oncologic Procedure; DNA biosynthesis; Development; Disease; Drug Carriers; Drug Delivery Systems; Drug Kinetics; Esters; Exhibits; Failure; Fluorouracil; Folate; Future; Goals; H1299; Head; In Vitro; Individual; Length; Ligands; Malignant Neoplasms; Methods; Molecular Weight; Morphology; Multi-Drug Resistance; Nanotechnology; P-Glycoprotein; Paclitaxel; Pharmaceutical Preparations; Phase; Play; Polyethylene Glycols; Public Health; Reporting; Research Proposals; Resistance; Role; Shapes; Structure; Succinates; Surface; Surface Properties; Technology; Therapeutic; Thymidylate Synthase Inhibitor; Time; Toxic effect; Treatment Efficacy; Water; analog; base; cancer cell; cancer therapy; design; folate-binding protein; in vivo; inhibitor/antagonist; killings; nanocrystal; nanodrug; nanoparticle; neoplastic cell; novel; retinal rods; sigma receptors; surfactant; tumor; uptake

DESCRIPTION (provided by applicant): Recently, we have developed nanocrystals capable of delivering anticancer drugs. These nanocrystals with possess low toxicity, high drug loading ratio, and overcome multidrug resistance (MDR) in cancer cells in vitro and in vivo. The overall goal of this research proposal is to further develop and investigate multifunctional nanocrystals for MDR cancer therapy. The scientific basis for this proposal originated from our three-phase nanoparticle engineering (3PNE) method recently developed, which includes phase 1, amorphous precipitate; phase 2, hydrated amorphous aggregate; and phase 3, stabilized nanocrystals (NCs). The 3PNE has been applied to the development of rod-shaped NCs for effective anticancer drug delivery. To achieve this goal, we propose three aims: specific aim 1, to examine the mechanisms of the NCs for their ability to enhance physical stability, overcome MDR, and their in vivo behavior; specific aim 2, to develop NCs that carry target ligands to deliver PTX to tumor; and specific aim 3, to establish the NCs for co-delivering a hydrophobic drug (i.e., Paclitaxel) and a hydrophilic anti-cancer drug (i.e., 5-fluorouracil) to synergistically kill tumor cells through different cellular mechanisms. Accomplishing these specific aims will further develop efficient nano-drug carriers for the treatment of cancer, particularly MDR cancer. PUBLIC HEALTH RELEVANCE: This project is relevant to cancer therapy in public health in two ways. First, it has the potential to develop novel nanocrystals (NCs) as an anticancer drug carrier for the efficient treatment of multidrug resistance (MDR) in cancer. Moreover, if successful, the development of new NCs in this proposal has the potential to deliver hydrophobic drugs for the treatment other diseases.

描述（由申请人提供）：最近，我们开发了能够输送抗癌药物的纳米晶体。这些纳米晶体具有低毒性，高药物负荷比并克服体外和体内癌细胞中多药耐药性（MDR）。该研究建议的总体目标是进一步开发和研究用于MDR癌症治疗的多功能纳米晶体。该提案的科学基础源自我们最近开发的三相纳米颗粒工程（3pne）方法，其中包括第1阶段，无定形沉淀；第2阶段，水合无定形骨料；和第3阶段，稳定的纳米晶体（NCS）。 3PNE已应用于杆状NC的开发，以进行有效的抗癌药物递送。为了实现这一目标，我们提出了三个目标：特定目的1，检查NCS的机制，以提高身体稳定性，克服MDR及其体内行为；特定的目标2，开发携带靶配体以将PTX输送到肿瘤的NC；和特定的目标3，建立用于共同交付疏水性药物（即紫杉醇）和亲水性抗癌药物（即5-氟尿嘧啶）的NCS，以通过不同的细胞机制协同杀死肿瘤细胞。实现这些特定目标将进一步发展有效的纳米药物载体来治疗癌症，尤其是MDR癌。 公共卫生相关性：该项目通过两种方式与公共卫生的癌症治疗有关。首先，它具有开发新型纳米晶体（NC）作为癌症中多药耐药性（MDR）的抗癌药物载体的潜力。此外，如果成功的话，该提案中新的NC的发展有可能为治疗其他疾病提供疏水药物。