Nanocrystals for the Treatment of Multidrug Resistance in Cancer

描述（由申请人提供）：最近，我们开发了能够传递抗癌药物的纳米晶体。这些纳米晶体具有低毒性、高载药比、在体外和体内克服癌细胞多药耐药（MDR）等特点。本研究计划的总体目标是进一步开发和研究多功能纳米晶体用于耐多药癌症治疗。这一建议的科学基础源于我们最近开发的三相纳米颗粒工程（3PNE）方法，其中包括相1，非晶沉淀；阶段2，水化非晶骨料；第三阶段是稳定纳米晶体（NCs）。3PNE已被应用于杆状纳米细胞的开发，用于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增强物理稳定性、克服耐多药的能力及其体内行为的机制；特异性目标2，开发携带靶配体的nc，将PTX传递到肿瘤；具体目标3，建立共同递送疏水药物（如紫杉醇）和亲水抗癌药物（如5-氟尿嘧啶）的nc，通过不同的细胞机制协同杀死肿瘤细胞。实现这些特定目标将进一步开发有效的纳米药物载体，用于治疗癌症，特别是耐多药癌症。

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.