Department of Biosciences, Integral University, Lucknow, India.
Division of Toxicology, CSIR-Central Drug Research Institute, Lucknow, India.
Int J Neurosci. 2021 Jun;131(6):591-598. doi: 10.1080/00207454.2020.1750393. Epub 2020 Apr 19.
Glioblastoma multiforme (GBM) is the most severe forms of brain cancer, eventually becoming the leading cause of brain cancer-related death worldwide. Owing to the bleak surgical interventions and resistance to the different treatment regime, GBM is a parlous disease demanding newer therapeutical perspective for its treatment. Toll-like receptors (TLRs) are well-known members of pathogen recognition receptors (PRRs) and have been extensively explored for their therapeutic and prophylactic potential in an array of disease including cancer. Recent trends in drug delivery research has shown shift towards delivering short DNA sequences (CpG DNA) to endosomal TLR9 within immune cells (macrophages, dendritic cells, etc.) for the activation of desired inflammatory response using non-agonistic β-glucan particles; a well-known ligand for Dectin-1 receptors. Our study is therefore focused to explore the role of nano-encapsulated CpG ODN as critical players in polarizing M2 scavenging to much desired pro-inflammatory type.
The nanoparticles entrapping CpG ODN 1826 were prepared by using a fungal polymer Schizophyllan (SPG). The constructed nanoparticles were characterized and assessed for their efficacy on rat glioblastoma cells (C6).
The constructed Schizophyllan (SPG) nanoparticles entrapping CpG ODN 1826 (95.3%) were of 25.49 nm in diameter and thus capable of crossing blood-brain barrier. The rat glioblastoma (C6) cells evaluated for intracellular oxidative burst and cytokine levels pre- and post-incubation with nanoparticles exhibited marked elevation in the expression of intracellular ROS and IFN-γ as well as IL-1β post treatment.
The findings indicate towards potentiality of repolarizing the M2 macrophages to much desired M1 phase by inducing higgh levels of oxidative burst and inflammatory cytokines. Consequently, the apoptosis was induced in glioblastoma cells establishing the suitablity of CpG ODN carrying nanoformulations as emerging therapeutic intervention for GBM.
多形性胶质母细胞瘤（GBM）是最严重的脑癌形式，最终成为全球脑癌相关死亡的主要原因。由于手术干预效果不佳以及对不同治疗方案的耐药性，GBM 是一种危险的疾病，需要新的治疗方法。 Toll 样受体（TLR）是病原体识别受体（PRR）的知名成员，已广泛探索其在多种疾病（包括癌症）中的治疗和预防潜力。最近药物输送研究的趋势表明，人们越来越关注将短 DNA 序列（CpG DNA）递送至免疫细胞（巨噬细胞、树突状细胞等）内的内体 TLR9，使用非激动剂β-葡聚糖颗粒作为 Dectin-1 受体的已知配体，从而激活所需的炎症反应。因此，我们的研究旨在探索纳米封装 CpG ODN 在将 M2 吞噬细胞极化到所需的促炎型中的作用。
用真菌聚合物裂褶菌聚糖（SPG）制备包封 CpG ODN 1826 的纳米颗粒。对构建的纳米颗粒进行了表征，并评估了其对大鼠神经胶质瘤细胞（C6）的疗效。
构建的裂褶菌聚糖（SPG）纳米颗粒包封 CpG ODN 1826（95.3%）的直径为 25.49nm，因此能够穿过血脑屏障。评估大鼠神经胶质瘤（C6）细胞在与纳米颗粒孵育前后的细胞内氧化爆发和细胞因子水平，结果显示，处理后细胞内 ROS 和 IFN-γ以及 IL-1β的表达明显升高。
这些发现表明，通过诱导高水平的氧化爆发和炎症细胞因子，有可能将 M2 巨噬细胞重新极化到所需的 M1 期。因此，在神经胶质瘤细胞中诱导了细胞凋亡，证明了携带 CpG ODN 的纳米制剂作为 GBM 新兴治疗干预措施的适用性。
