载姜黄素壳聚糖海藻酸钠纳米球对 KMBC-10 球体细胞系的细胞毒性作用。

PURPOSE: Breast cancer is one of the most lethal types of cancer in women. Curcumin showed therapeutic potential against breast cancer, but applying that by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. Moreover, poor water solubility of curcumin causes accumulation of a high concentration of curcumin and so decrease its permeability to the cell. Many strategies are employed to reduce curcumin metabolism such as adjuvants and designing novel delivery systems. Therefore, in this study sodium alginate and chitosan were used to synthesize the hydrogels that are known as biocompatible, hydrophilic and low toxic drug delivery systems. Also, folic acid was used to link to chitosan in order to actively targetfolate receptors on the cells. METHODS: Chitosan-β-cyclodextrin-TPP-Folic acid/alginate nanoparticles were synthesized and then curcumin was loaded on them. Interaction between the constituents of the particles was characterized by FTIR spectroscopy. Morphological structures of samples were studied by FE-SEM. Release profile of curcumin was determined by dialysis membrane. The cytotoxic test was done on the Kerman male breast cancer (KMBC-10) cell line by using MTT assay. The viability of cells was detected by fluorescent staining. Gene expression was investigated by real-time PCR. RESULTS: The encapsulation of curcumin into nano-particles showed an almost spherical shape and an average particle size of 155 nm. In vitro cytotoxicity investigation was indicated as dose-respond reaction against cancer breast cells after 24 h incubation. On the other hand, in vitro cell uptake study revealed active targeting of CUR-NPs into spheroids. Besides, expression was detected about 30-fold less than curcumin alone. The CUR-NPs inhibited proliferation and increased apoptosis in spheroid human breast cancer cells. CONCLUSION: Our results showed the potential of NPs as an effective candidate for curcumin delivery to the target tumor spheroids that confirmed the creatable role of folate receptors.

目的：乳腺癌是女性最致命的癌症类型之一。姜黄素在治疗乳腺癌方面显示出了潜力，但由于其生物利用度差，单独应用并不会带来相关的健康益处，这主要是由于其吸收不良、代谢迅速和消除迅速。此外，姜黄素的低水溶性导致其在细胞内的通透性降低。为了减少姜黄素的代谢，人们采用了许多策略，如使用佐剂和设计新型的递送系统。因此，在本研究中，我们使用海藻酸钠和壳聚糖来合成水凝胶，这些水凝胶被认为是生物相容的、亲水性的和低毒的药物递送系统。此外，还使用叶酸将其连接到壳聚糖上，以主动靶向细胞表面的叶酸受体。

方法：合成了壳聚糖-β-环糊精-TPP-叶酸/海藻酸钠纳米粒子，然后将姜黄素负载在其上。通过傅里叶变换红外光谱法对粒子成分之间的相互作用进行了表征。通过 FE-SEM 研究了样品的形貌结构。通过透析膜测定了姜黄素的释放曲线。采用 MTT 法在 Kerman 男性乳腺癌（KMBC-10）细胞系上进行了姜黄素的细胞毒性试验。通过荧光染色检测细胞活力。采用实时 PCR 法检测基因表达。

结果：姜黄素包封在纳米粒子中呈现出几乎球形的形状，平均粒径为 155nm。体外细胞毒性研究表明，在 24 小时孵育后，对乳腺癌细胞呈剂量反应。另一方面，体外细胞摄取研究表明，CUR-NPs 可以主动靶向进入球体。此外，与单独使用姜黄素相比，CUR-NPs 使表达降低了约 30 倍。CUR-NPs 抑制了球体人乳腺癌细胞的增殖并增加了细胞凋亡。

结论：我们的研究结果表明，NPs 作为姜黄素向靶肿瘤球体传递的有效候选物具有潜力，这证实了叶酸受体的可创建作用。