D'Angelo Edoardo, Rampado Riccardo, Sensi Francesca, Marangio Asia, Rossi Anna De, Repetto Ombretta, Steffan Agostino, Corallo Diana, Aveic Sanja, Bianchi Gaia, Collino Federica, Caliceti Paolo, Spolverato Gaya, Agostini Marco
General Surgery 3, Department of Surgery, Oncology and Gastroenterology, University of Padova, via Giustiniani 2, 35128 Padua, Italy; NanoInspired Biomedicine Lab, Fondazione Istituto di Ricerca Pediatrica Città della Speranza, Padua, Italy.
Laboratory of Precision Nanomedicine, Shmunis School of Biomedicine and Cancer, Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel; Department of Materials Sciences and Engineering, Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv, Israel; Center for Nanoscience and Nanotechnology, Tel Aviv University, Tel Aviv, Israel; Cancer Biology Research Center, Tel Aviv University, Tel Aviv, Israel; Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Via F. Marzolo 5, 35131 Padua, Italy.
Int J Pharm. 2025 Feb 10;670:125169. doi: 10.1016/j.ijpharm.2025.125169. Epub 2025 Jan 3.
Macrophages are a pivotal immune cell population in the tumor microenvironment of colorectal cancer (CRC). Differently-polarized macrophages could be exploited to yield naturally-tailored biomimetic nanoparticles for CRC targeting. Here, membrane proteins were isolated from the THP-1 cell line, and anti-tumor macrophages (M1) were obtained from differentiation of THP-1. Membrane proteins were isolated from THP-1 and M1 and used to produce lipid nanovesicles (LNVs; T-LNVs and M1-LNVs) by microfluidic process, which were loaded with doxorubicin (DOXO). The DOXO loaded T-LNVs and M1-LNVs showed similar size (120-145 nm), PDI (0.11-0.28), zeta potential (-15 to -30 mV) and drug loading efficiency (65-75 %). Mass-spectrometry confirmed the presence of the membrane proteins in the LNVs. The abundance of proteins related to stealth properties, cancer targeting, endothelial adhesion and immune-related markers was significantly different in T-LNVs and M1-LNVs. Cell culture studies showed that M1-LNVs possessed higher cancer cell targeting, uptake and cytotoxicity compared to T-LNVs. In vivo studies performed with zebrafish embryos showed that M1-LNVs yielded higher cancer cell targeting and cytotoxicity while systemic cytotoxicity was lower compared to free DOXO. These findings confirm the potentiality and versatility of M1-LNVs for cancer treatment, which could be exploited as new avenue of nanoparticles-based therapies for precision medicine.
巨噬细胞是结直肠癌（CRC）肿瘤微环境中的关键免疫细胞群体。不同极化的巨噬细胞可用于制备天然定制的仿生纳米颗粒，用于靶向CRC。在这里，从THP-1细胞系中分离膜蛋白，并通过THP-1分化获得抗肿瘤巨噬细胞（M1）。从THP-1和M1中分离膜蛋白，并通过微流控工艺用于生产脂质纳米囊泡（LNVs；T-LNVs和M1-LNVs），这些纳米囊泡负载了阿霉素（DOXO）。负载DOXO的T-LNVs和M1-LNVs显示出相似的尺寸（120-145nm）、多分散指数（0.11-0.28）、zeta电位（-15至-30mV）和载药效率（65-75%）。质谱分析证实了LNVs中存在膜蛋白。与隐形特性、癌症靶向、内皮粘附和免疫相关标志物相关的蛋白质丰度在T-LNVs和M1-LNVs中有显著差异。细胞培养研究表明，与T-LNVs相比，M1-LNVs具有更高的癌细胞靶向性、摄取率和细胞毒性。对斑马鱼胚胎进行的体内研究表明，与游离DOXO相比，M1-LNVs具有更高的癌细胞靶向性和细胞毒性，而全身细胞毒性更低。这些发现证实了M1-LNVs在癌症治疗中的潜力和多功能性，可作为基于纳米颗粒的精准医学治疗新途径加以利用。
