Nanocrystals for the Treatment of Multidrug Resistance in Cancer

描述（由申请人提供）：最近，我们开发了能够递送抗癌药物的纳米晶体。这些纳米晶具有低毒性、高载药率和克服肿瘤细胞体内外多药耐药（MDR）的能力。这项研究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。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（3 PNE）方法，其中包括第1阶段，无定形沉淀物;第2阶段，水合无定形聚集体;和第3阶段，稳定的纳米晶体（NC）。3 PNE已被应用于开发用于有效抗癌药物递送的棒状NC。为了实现这一目标，我们提出了三个目标：具体目标1，检查NC增强物理稳定性、克服MDR的能力及其体内行为的机制;具体目标2，开发携带靶配体以将PTX递送至肿瘤的NC;以及具体目标3，建立用于共递送疏水药物（即，紫杉醇）和亲水性抗癌药物（即，5-氟尿嘧啶）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用于治疗癌症，特别是MDR癌症的有效纳米药物载体。

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.