Tiradentes University - UNIT, Av. Murilo Dantas 300, 49032-490 Aracaju, SE, Brazil; Institute of Technology and Research - ITP, Av. Murilo Dantas 300, 49032-490 Aracaju, SE, Brazil.
Department of Food Engineering, URI - Erechim Av. Sete de Setembro, 1621, 99709-910 Erechim, Rio Grande do Sul, Brazil.
Mater Sci Eng C Mater Biol Appl. 2021 May;124:112089. doi: 10.1016/j.msec.2021.112089. Epub 2021 Mar 31.
Indole-3-carbinol (I3C) is a plant molecule known to be active against several types of cancer, but some chemical characteristics limit its clinical applications. In order to overcome these limitations, polymeric nanoparticles can be used as carrier systems for targeted delivery of I3C. In this study, chitosan and chitosan/polyethylene glycol nanoparticles (CS NP and CS/PEG NP, respectively) were prepared to encapsulate I3C by ionic gelation method. The polymeric nanoparticles were characterized by Dynamic Scattering Light (DLS), Zeta Potential (ZP), Fourier Transform Infrared (FTIR) spetroscopy, X-Ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Field Emission Gun Scanning Electron Microscopy (FEG-SEM). I3C release testing was performed at an acidic media and the interactions between I3C and chitosan or PEG were evaluated by Density Functional Theory (DFT). Cytotoxicity of nanoparticles in bladder cancer T24 cell line was evaluated by the Methyl-thiazolyl-tetrazolium (MTT) colorimetric assay. The average size of the nanoparticles was observed to be in the range from 133.3 ± 3.7 nm to 180.4 ± 2.7 nm with a relatively homogeneous distribution. Samples had relatively high positive zeta potential values (between +20.3 ± 0.5 mV and + 24.3 ± 0.5 mV). Similar encapsulation efficiencies (about 80%) for both nanoparticles were obtained. Physicochemical and thermal characterizations pointed to the encapsulation of I3c. electron microscopy showed spherical particles with smooth or ragged surface characteristics, depending on the presence of PEG. The mathematical fitting of the release profile demonstrated that I3C-CS NP followed the Higuchi model whereas I3C-CS/PEG NP the Korsmeyer-Peppas model. Chemical differences between the nanoparticles as based on the I3C/CS or I3C/PEG interactions were demonstrate by computational characterization. The assessment of cell viability by the MTT test showed that the presence of both free I3C and I3C-loaded nanoparticles lead to statistically significant reduction in T24 cells viability in the concentrations from 500 to 2000 μM, when comparison to the control group after 24 h of exposure. Thus, CS and CS/PEG nanoparticles present as feasible I3C carrier systems for cancer therapy.
吲哚-3-甲醇（I3C）是一种已知对多种类型癌症具有活性的植物分子，但一些化学特性限制了其临床应用。为了克服这些限制，可以使用聚合物纳米粒子作为 I3C 靶向递药的载体系统。在这项研究中，壳聚糖和壳聚糖/聚乙二醇纳米粒子（CS NP 和 CS/PEG NP）分别通过离子凝胶法制备以包封 I3C。通过动态光散射（DLS）、Zeta 电位（ZP）、傅里叶变换红外（FTIR）光谱、X 射线衍射（XRD）、热重分析（TGA）、差示扫描量热法（DSC）和场发射枪扫描电子显微镜（FEG-SEM）对聚合物纳米粒子进行了表征。在酸性介质中进行了 I3C 释放测试，并通过密度泛函理论（DFT）评估了 I3C 与壳聚糖或 PEG 之间的相互作用。通过甲基噻唑基四唑（MTT）比色法评估了纳米粒子在膀胱癌 T24 细胞系中的细胞毒性。纳米粒子的平均粒径观察在 133.3±3.7nm 至 180.4±2.7nm 范围内，分布较为均匀。样品具有相对较高的正 Zeta 电位值（在+20.3±0.5mV 和+24.3±0.5mV 之间）。两种纳米粒子的包封效率（约 80%）相近。物理化学和热特性表明 I3c 被包封。电子显微镜显示出具有光滑或粗糙表面特征的球形颗粒，这取决于 PEG 的存在。释放曲线的数学拟合表明，I3C-CS NP 遵循 Higuchi 模型，而 I3C-CS/PEG NP 遵循 Korsmeyer-Peppas 模型。基于 I3C/CS 或 I3C/PEG 相互作用的纳米粒子的化学差异通过计算特性得到证明。通过 MTT 试验评估细胞活力的结果表明，与对照组相比，在 500 至 2000μM 的浓度下，游离 I3C 和负载 I3C 的纳米粒子均导致 T24 细胞活力显著降低，在暴露 24 小时后。因此，CS 和 CS/PEG 纳米粒子可用作癌症治疗的可行 I3C 载体系统。
