文献：

Mithramycin-loaded mPEG-PLGA nanoparticles exert potent antitumor efficacy against pancreatic carcinoma

文献链接：

https://pubmed.ncbi.nlm.nih.gov/28769562/

作者：

Xu-Jie Liu, Liang Li, Xiu-Jun Liu, Yi Li , Chun-Yan Zhao, Rui-Qi Wang , Yong-Su Zhen

相关产品：

聚(乙二醇)甲醚-嵌段-聚（丙交酯-共-乙交酯） PLGA-MPEG

原文摘要：

Previous studies have shown that mithramycin A (MIT) is a promising candidate for the treatment of pancreatic carcinoma through inhibiting transcription factor Sp1. However, systemic toxicities may limit its clinical application. Here, we report a rationally designed formulation of MIT-loaded nanoparticles (MIT-NPs) with a small size and sustained release for improved passive targeting and enhanced therapeutic efficacy. At a well-tolerated dose of 2 mg/kg, MIT-NPs suppressed BxPC-3 tumor growth by 96%. Compared at an equivalent dose, MIT-NPs exerted significantly higher therapeutic effect than free MIT (86% versus 51%, P<0.01). Moreover, the treatment of MIT and MIT-NPs reduced the expression level of oncogene c-Myc regulated by Sp1, and notably, both of them decreased the protein level of CD47. In summary, the novel formulation of MIT-NPs shows highly therapeutic efficacy against pancreatic carcinoma xenograft. In addition, MIT-NPs can downregulate CD47 expression, implying that it might play a positive role in cancer immunotherapy.

本文献设计了一个纳米载药技术。将药物MIT封装到了一种特殊的纳米颗粒载体中，这种载体是由甲氧基聚乙二醇-嵌段聚（d，l-丙交酯-共-乙醇酸）（mPEG-PLGA）构成的。mPEG-PLGA是一种具有良好生物相容性和生物可降解性的聚合物材料，能够有效保护药物在体内的稳定性，并且可以实现药物的缓慢释放，从而延长药物的作用时间。

图为：聚(乙二醇)甲醚-嵌段-聚（丙交酯-共-乙交酯） PLGA-MPEG结构式

MIT负载纳米颗粒（MIT NPs）制剂具有小尺寸和缓释性，可改善被动靶向。通过将MIT封装到载药的甲氧基聚乙二醇-嵌段聚（d，l-丙交酯-共-乙醇酸）（mPEG-PLGA）纳米颗粒中，制备了近球形MIT NPs。MIT NPs的体外释放以缓释模式持续>48小时。通过流式细胞术和共聚焦显微镜测定，NPs快速有效地内化到细胞中，在1-2小时达到峰值水平。通过制备工艺，制备出的近球形的MIT纳米颗粒（MIT NPs）。这种近球形的结构不仅有助于提高纳米颗粒的分散性，还能增强其在体内的循环能力和靶向性能，使其能够更有效地将药物输送到病变部位，发挥药物的效果。

体内荧光成像显示，制备的NPs在BxPC-3和MIA-Paca-2异种移植物中逐渐积累并保留168小时。BxPC-30和MIA-Paca-2Tumor 中的荧光强度远强于各种测试器官的荧光强度。MIT NPs的新制剂对胰腺Cancer异种移植物显示出高度的Treatment效果。此外，MIT-NP可下调CD47的表达，可以发挥积极作用。