Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei 430071, P.R. China.
Department of Chemistry, Key Laboratory of Biomedical Polymers of Ministry of Education, Wuhan University, Wuhan, Hubei 430072, P.R. China.
Oncol Rep. 2021 Feb;45(2):547-556. doi: 10.3892/or.2020.7871. Epub 2020 Nov 27.
Gliomas are one of the most common types of primary brain tumors. Despite recent advances in the combination of surgery, radiotherapy, systemic therapy (chemotherapy, targeted therapy) and supportive therapy in the multimodal treatment of gliomas, the overall prognosis remains poor and the long‑term survival rate is low. Thus, it is crucial to develop a novel glioma management method. Due to its relatively non‑invasive, selective and repeatable characteristics, photodynamic therapy (PDT) has been investigated for glioma therapy in the past decade, exhibiting higher selectivity and lower side effects compared with those of conventional therapy. However, most of the photosensitizers (PSs) are highly hydrophobic, leading to poor water solubility, rapid degradation with clearance in blood circulation and ultimately, low bioavailability. In the present study, hydrophilic polyethylene glycol (PEG)‑chlorin e6 (Ce6) chelated gadolinium ion (Gd3+) nanoparticles (PEG‑Ce6‑Gd NPs) were synthesized via a chelation and self‑assembly process. Initially, the cell cytotoxicity of PEG‑Ce6‑Gd NPs was evaluated with or without laser irradiation. The in vitro study demonstrated the lack of toxicity of PEG‑Ce6‑Gd NPs to tumor cells in the absence of laser irradiation. However, its toxicity was enhanced under laser irradiation. Moreover, the size and weight of brain tumors were significantly decreased in mice with glioma xenografts, which was further confirmed via histological analysis. Subsequently, the results indicated that the PEG‑Ce6‑Gd NPs had a favorable T1‑weighted contrast performance (0.43 mg ml‑1 s‑1) and were observed to have significant contrast enhancement at the tumor site from 0.25 to 1 h post‑injection in vivo. The favorable MRI, as well as the synergetic photodynamic antitumor effect and antineoplastic ability of PEG‑Ce6‑Gd NPs was identified. It was suggested that PEG‑Ce6‑Gd NPs had great potential in the diagnosis and PDT treatment of gliomas, and possibly other cancer types, with prospects of clinical application in the near future.
神经胶质瘤是最常见的原发性脑肿瘤之一。尽管在多模式治疗神经胶质瘤中，手术、放疗、系统治疗（化疗、靶向治疗）和支持治疗的联合应用取得了近期进展，但总体预后仍然较差，长期生存率较低。因此，开发新的神经胶质瘤治疗方法至关重要。由于光动力疗法（PDT）具有相对非侵入性、选择性和可重复性的特点，在过去十年中，PDT 已被用于神经胶质瘤的治疗研究，与传统治疗相比，其具有更高的选择性和更低的副作用。然而，大多数光敏剂（PSs）具有较强的疏水性，导致其水溶性差，在血液循环中迅速降解并最终生物利用度低。本研究通过螯合和自组装过程合成了亲水性聚乙二醇（PEG）-氯代卟啉 e6（Ce6）螯合钆离子（Gd3+）纳米颗粒（PEG-Ce6-Gd NPs）。首先，评估了有无激光照射时 PEG-Ce6-Gd NPs 的细胞细胞毒性。体外研究表明，在没有激光照射的情况下，PEG-Ce6-Gd NPs 对肿瘤细胞没有毒性。然而，在激光照射下，其毒性增强。此外，在荷神经胶质瘤异种移植小鼠中，肿瘤的大小和重量明显减小，组织学分析进一步证实了这一点。随后，结果表明 PEG-Ce6-Gd NPs 具有良好的 T1 加权对比性能（0.43mgml-1s-1），在体内注射后 0.25-1h 时在肿瘤部位观察到明显的对比增强。确定了具有良好 MRI 性能以及协同光动力抗肿瘤作用和抗瘤能力的 PEG-Ce6-Gd NPs。提示 PEG-Ce6-Gd NPs 具有在神经胶质瘤以及其他癌症类型的诊断和 PDT 治疗方面的巨大潜力，有望在不久的将来在临床上应用。
