研究动态
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多模式靶向剂“磷酸化半乳糖基化壳聚糖包覆磁性纳米粒子”对 N-亚硝基二乙胺诱导的肝细胞癌的抗癌治疗潜力。

Anticancer therapeutic potential of multimodal targeting agent- "phosphorylated galactosylated chitosan coated magnetic nanoparticles" against N-nitrosodiethylamine-induced hepatocellular carcinoma.

发表日期:2024 Jul 11
作者: Anushree Udupi, Sachin Shetty, Jesil Mathew Aranjani, Rajesh Kumar, Sanjay Bharati
来源: ANTIOXIDANTS & REDOX SIGNALING

摘要:

超顺磁性氧化铁纳米颗粒(SPIONs)广泛用作靶向药物递送的载体,在磁热疗、化学动力学治疗和磁辅助放射性核素治疗领域具有多种优势。 SPION的特性可以定制,通过“被动靶向”将药物输送到肿瘤中,它们还可以涂上组织特异性药物,通过“主动靶向”增强肿瘤的摄取。在我们早期的研究中,我们开发了HCC特异性靶向剂——“磷酸化半乳糖基化壳聚糖”(PGC),用于靶向脱唾液酸糖蛋白受体。考虑到他们令人鼓舞的结果,在这项研究中,我们开发了一种用于靶向 HCC 的多功能靶向系统——“磷酸化半乳糖基化壳聚糖包被的磁性纳米粒子”(PGCMNPs)。采用共沉淀法合成了PGCMNPs,并通过DLS、XRD、TEM、VSM、元素分析和FT-IR光谱进行了表征。评估了 PGCMNP 的体外抗氧化特性、HepG2 细胞的摄取、生物分布、体内毒性,并评估了小鼠模型中 NDEA 诱导的 HCC 的抗癌治疗潜力,包括肿瘤状态、电特性、抗氧化防御状态和细胞凋亡。表征研究证实了具有超顺磁性的 PGCMNP 的成功形成。内化研究表明 HepG2 细胞中 PGCMNP 的摄取率为 (99-100)%。这些结果也得到了生物分布研究的支持,其中注意到肝细胞内铁含量增加(296%)。此外,PGCMNPs 没有表现出体内毒性。通过观察,PGCMNPs 治疗减少了荷瘤动物的数量 (41.6%),并显着 (p≤0.05) 降低了肿瘤的多重性,其抗癌治疗潜力是显而易见的。总体而言,这项研究表明,具有改进特性的 PGCMNP 可以被肝癌细胞有效吸收,并且具有治疗 HCC 的潜力。此外,该药物可以用 32P 标记,因此可以通过放射消融和磁热疗提供多模式癌症治疗选择。© 2024。作者。
Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively used as carriers in targeted drug delivery and has several advantages in the field of magnetic hyperthermia, chemodynamic therapy and magnet assisted radionuclide therapy. The characteristics of SPIONs can be tailored to deliver drugs into tumor via "passive targeting" and they can also be coated with tissue-specific agents to enhance tumor uptake via "active targeting". In our earlier studies, we developed HCC specific targeting agent- "phosphorylated galactosylated chitosan"(PGC) for targeting asialoglycoprotein receptors. Considering their encouraging results, in this study we developed a multifunctional targeting system- "phosphorylated galactosylated chitosan-coated magnetic nanoparticles"(PGCMNPs) for targeting HCC. PGCMNPs were synthesized by co-precipitation method and characterized by DLS, XRD, TEM, VSM, elemental analysis and FT-IR spectroscopy. PGCMNPs were evaluated for in vitro antioxidant properties, uptake in HepG2 cells, biodistribution, in vivo toxicity and were also evaluated for anticancer therapeutic potential against NDEA-induced HCC in mice model in terms of tumor status, electrical properties, antioxidant defense status and apoptosis. The characterization studies confirmed successful formation of PGCMNPs with superparamagnetic properties. The internalization studies demonstrated (99-100)% uptake of PGCMNPs in HepG2 cells. These results were also supported by biodistribution studies in which increased iron content (296%) was noted inside the hepatocytes. Further, PGCMNPs exhibited no in vivo toxicity. The anticancer therapeutic potential was evident from observation that PGCMNPs treatment decreased tumor bearing animals (41.6%) and significantly (p ≤ 0.05) lowered tumor multiplicity. Overall, this study indicated that PGCMNPs with improved properties are efficiently taken-up by hepatoma cells and has therapeutic potential against HCC. Further, this agent can be tagged with 32P and hence can offer multimodal cancer treatment options via radiation ablation as well as magnetic hyperthermia.© 2024. The Author(s).