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: 8680176
• 负责人: Leaf Huang
• 金额: $ 29.79万
• 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/8680176
• 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.

描述（申请人提供）：最近，我们开发了能够递送抗癌药物的纳米晶体。这些纳米晶体具有低毒性、高载药率，并克服了体外和体内癌细胞的多药耐药性（MDR）。该研究计划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。该提议的科学依据源于我们最近开发的三相纳米颗粒工程（3PNE）方法，其中包括第一相，无定形沉淀；第2相，水合无定形骨料；第三相，稳定纳米晶体 (NC)。 3PNE 已应用于棒状 NC 的开发，以实现有效的抗癌药物输送。为了实现这一目标，我们提出了三个目标：具体目标1，研究NCs增强身体稳定性、克服MDR的能力及其体内行为的机制；具体目标2，开发携带靶配体的NC，将PTX递送至肿瘤；具体目标3，建立共同递送疏水性药物（即紫杉醇）和亲水性抗癌药物（即5-氟尿嘧啶）的NC，通过不同的细胞机制协同杀死肿瘤细胞。实现这些具体目标将进一步开发有效的纳米药物载体来治疗癌症，特别是耐多药癌症。