Research Center for Functional Materials, National Institute for Materials Science (NIMS), 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Mansoura University, 60 El Gomhouria St., Mansoura, Dakahlia Governorate 35516, Egypt.
Molecules. 2020 Sep 29;25(19):4467. doi: 10.3390/molecules25194467.
Titanium dioxide nanoparticles (TiO NPs) have a strong potential for cancer therapeutic and bioimaging applications such as photodynamic therapy (PDT) and photodynamic diagnosis (PDD). Our previous results have shown that TiO NPs have a low cellular uptake and can induce cell proliferation. This suggests that TiO NPs could increase the risk of tumor overgrowth while being used for PDD and PDT. To solve this problem, we constructed epidermal growth factor-ligated polyethylene glycol-coated TiO NPs (EGF-TiO PEG NPs). In this work, we studied the effect of EGF conjugation on the cellular uptake of TiO PEG NPs. Then, we investigated the effect of both non-conjugated and EGF-TiO PEG NPs on the A431 epidermal cancer cell line, proliferation and growth via the investigation of EGFR localization and expression. Our results indicated that TiO PEG NPs induced EGFRs aggregation on the A431 cells surface and induced cell proliferation. In addition, EGF-TiO PEG NPs induced the internalization of EGFRs inside of cells with increased cellular NPs uptake and decreased cellular proliferation compared to TiO PEG NPs-treated cells. These findings suggest that EGF conjugation can increase the efficacy of TiO PEG NPs for biomedical applications such as PDD and PDT with decreased risk of tumor overgrowth.
二氧化钛纳米粒子(TiO NPs)在癌症治疗和生物成像应用方面具有很强的潜力,如光动力疗法(PDT)和光动力诊断(PDD)。我们之前的研究结果表明,TiO NPs 的细胞摄取率较低,并能诱导细胞增殖。这表明,TiO NPs 在用于 PDD 和 PDT 时,可能会增加肿瘤过度生长的风险。为了解决这个问题,我们构建了表皮生长因子连接的聚乙二醇包覆的 TiO NPs(EGF-TiO PEG NPs)。在这项工作中,我们研究了 EGF 连接对 TiO PEG NPs 细胞摄取的影响。然后,我们通过研究 EGFR 定位和表达,研究了非共轭和 EGF-TiO PEG NPs 对 A431 表皮癌细胞系增殖和生长的影响。我们的结果表明,TiO PEG NPs 诱导 EGFRs 在 A431 细胞表面聚集,并诱导细胞增殖。此外,与 TiO PEG NPs 处理的细胞相比,EGF-TiO PEG NPs 诱导 EGFRs 内化到细胞内,增加了细胞内 NPs 的摄取,降低了细胞增殖。这些发现表明,EGF 连接可以提高 TiO PEG NPs 在 PDD 和 PDT 等生物医学应用中的疗效,同时降低肿瘤过度生长的风险。