Alves Luiz Anastacio, Ferreira Leonardo Braga, Pacheco Paulo Furtado, Mendivelso Edith Alejandra Carreño, Teixeira Pedro Celso Nogueira, Faria Robson Xavier
Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz-FIOCRUZ, 21045-900, Rio de Janeiro, RJ, Brasil.
Laboratório de Inflamação e Instituto Oswaldo Cruz, Fundação Oswaldo Cruz-FIOCRUZ, 21045-900, Rio de Janeiro, RJ, Brasil.
Oncotarget. 2018 May 18;9(38):25342-25354. doi: 10.18632/oncotarget.25150.
According to the World Health Organization (WHO), cancer is one of main causes of death worldwide, with 8.2 million people dying from this disease in 2012. Because of this, new forms of treatments or improvement of current treatments are crucial. In this regard, Photodynamic therapy (PDT) has been used to successfully treat cancers that can be easily accessed externally or by fibre-optic endoscopes, such as skin, bladder and esophagus cancers. In addition, this therapy can used alongside radiotherapy and chemotherapy in order to kill cancer cells. The main problem in implementing PDT is penetration of visible light deeper than 10 mm in tissues, due to scattering and absorption by tissue chromophores. Unfortunately, this excludes several internal organs affected by cancer. Another issue in this regard is the use of a selective cancer cell-photosensitizing compound. Nevertheless, several groups have recently developed scintillation nanoparticles, which can be stimulated by X-rays, thereby making this a possible solution for light production in deeper tissues. Alternative approaches have also been developed, such as photosensitizer structure modifications and cell membrane permeabilizing agents. In this context, certain channels lead to transitory plasma membrane permeability changes, such as pannexin, connexin hemmichannels, TRPV1-4 and P2×7, which allow for the non-selective passage of molecules up to 1,000 Da. Herein, we discuss the particular case of the P2×7 receptor-associated pore as a drug delivery system for hydrophilic substances to be applied in PDT, which could also be carried out with other channels. Methylene blue (MB) is a low cost dye used as a prototype photosensitizer, approved for clinical use in several other clinical conditions, as well as photodynamic therapy for fungi infections.
根据世界卫生组织(WHO)的数据,癌症是全球主要死因之一,2012年有820万人死于该疾病。因此,新的治疗形式或现有治疗方法的改进至关重要。在这方面,光动力疗法(PDT)已被成功用于治疗可通过外部或纤维光学内窥镜轻松触及的癌症,如皮肤癌、膀胱癌和食道癌。此外,这种疗法可与放疗和化疗联合使用以杀死癌细胞。实施PDT的主要问题是由于组织发色团的散射和吸收,可见光在组织中的穿透深度超过10毫米。不幸的是,这排除了几个受癌症影响的内部器官。这方面的另一个问题是使用选择性癌细胞光敏化合物。然而,最近有几个研究小组开发了闪烁纳米颗粒,其可被X射线激发,从而使这成为在更深组织中产生光的一种可能解决方案。还开发了其他替代方法,如光敏剂结构修饰和细胞膜通透剂。在这种情况下,某些通道会导致瞬时质膜通透性变化,如泛连接蛋白、连接蛋白半通道、TRPV1 - 4和P2×7,它们允许分子量高达1000 Da的分子非选择性通过。在此,我们讨论与P2×7受体相关的孔作为用于亲水性物质的药物递送系统在PDT中的特殊情况,这也可以通过其他通道来实现。亚甲蓝(MB)是一种低成本染料,用作原型光敏剂,已被批准用于其他几种临床病症的临床治疗以及真菌感染的光动力治疗。