Karatug Kacar Ayse, Sak Rabia, Nurdogan Ayse Nur, Ergin Kızılcay Gamze, Bahadori Fatemeh
Department of Biology, Faculty of Science, Istanbul University, 34134, Vezneciler, Istanbul, Turkey.
Department of Medicinal Biochemistry, Institute of Health Sciences, Bezmialem Vakif University, Istanbul, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 22. doi: 10.1007/s00210-025-04455-7.
The study aimed to investigate the effects of dual-targeted poly-lactic-co-glycolic acid (PLGA) nanoparticles (NP) containing esculetin (ESC) and curcumin (CURC), coated with membrane and cytosolic proteins, isolated from PID-PC (pancreatic islet-derived precursor cells) and MIA PaCa-2 cells, on pancreatic cancer. MIA PaCa-2 cells' viability treated with different combinations of the above-mentioned molecules and proteins was investigated in vitro. The sizes of all formed nanoparticles were determined by the "dynamic light scattering" method. The drug release profile of drug-containing PLGA-NP was examined. Cell death percentages and ROS levels were analyzed. Naked ESC showed an IC50 of 45.226 µg, while PLGA-coated ESC showed no measurable IC50. For CURC, no IC50 was observed in its naked form, but PLGA-CURC induced cell death starting at 6.25 µg. In the PLGA_ESC + CURC group, IC50 values were 75 µg for ESC and 9.375 µg for CURC. PLGA-coated PID-PC cytoplasmic proteins reduced ESC-treated cell viability by 46.42%, while the PLGA-coated MIA PaCa-2 cytoplasmic protein with ESC + CURC was most effective (41.11%). PLGA_ESC was released in 48 h, but protein coating accelerated release to 6 h. CURC showed delayed release, reaching only 30% at 72 h. PID-PC membrane proteins enhanced and prolonged release; MIA PaCa-2 cytoplasmic proteins suppressed it. Necrosis increased in all groups, while apoptosis and ROS decreased except in the CURC-treated groups. The novel membrane and cytosolic protein-coated PLGA-NP designed by our group, for the first time, has provided significant results in the treatment of pancreatic cancer.
该研究旨在探究含有七叶亭（ESC）和姜黄素（CURC）的双靶向聚乳酸-乙醇酸共聚物（PLGA）纳米颗粒（NP）对胰腺癌的影响，这些纳米颗粒包被有从胰腺胰岛衍生前体细胞（PID-PC）和MIA PaCa-2细胞中分离出的膜蛋白和胞质蛋白。在体外研究了用上述分子和蛋白的不同组合处理后MIA PaCa-2细胞的活力。通过“动态光散射”方法测定所有形成的纳米颗粒的大小。检测了含药PLGA-NP的药物释放曲线。分析了细胞死亡百分比和活性氧水平。游离ESC的半数抑制浓度（IC50）为45.226μg，而PLGA包被的ESC未显示可测量的IC50。对于CURC，游离形式未观察到IC50，但PLGA-CURC从6.25μg开始诱导细胞死亡。在PLGA_ESC + CURC组中，ESC的IC50值为75μg，CURC的IC50值为9.375μg。PLGA包被的PID-PC胞质蛋白使ESC处理的细胞活力降低了46.42%，而PLGA包被的MIA PaCa-2胞质蛋白与ESC + CURC联合使用时效果最佳（41.11%）。PLGA_ESC在48小时内释放，但蛋白包被加速释放至6小时。CURC显示出延迟释放，在72小时时仅释放30%。PID-PC膜蛋白增强并延长了释放；MIA PaCa-2胞质蛋白则抑制了释放。所有组的坏死均增加，除了CURC处理组外，凋亡和活性氧均减少。我们团队设计的新型膜蛋白和胞质蛋白包被的PLGA-NP首次在胰腺癌治疗中取得了显著成果。
