Chen Guann-Tyng, Hu Teh-Min
Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Yangming Campus, Taipei 112, Taiwan.
Tri-Service General Hospital, Beitou-Branch, Taipei 112, Taiwan.
ACS Omega. 2021 Nov 16;6(47):32109-32119. doi: 10.1021/acsomega.1c04877. eCollection 2021 Nov 30.
Methylene blue (MB), a century-old drug and a fluorescent dye, has a long history of diverse applications, both in drug therapy and as a tissue-staining agent. However, MB is inherently unstable when exposed to light and reducing agents. In this study, we aim to prepare and characterize polysulfide-based organosilica colloidal particles for efficient, stable, and protective encapsulation of MB. Disulfide- and tetrasulfide-containing organosilane congeners were used as organosilica precursors for direct synthesis of organosilica colloids based on the silica ouzo effect. MB was spontaneously entrapped into the colloidal particles during the particle formation process. The following properties of the colloidal MB were evaluated: particle size, surface charge, atomic distribution, encapsulation efficiency, MB release, photodynamic activity, thiol and ascorbate reactivity, and cytotoxicity. The DLS measurements show that the size of colloidal MB is tunable in a range of 100 nm to 1 μm. SEM images reveal spherical particles with composition-dependent particle sizes of 70-120 nm (coefficient of variation: 15-18%). MB was encapsulated in the colloidal particles with a maximal efficiency of 95%. The release of MB from the colloids was <1% at 4 h and <3.5% at 48 h. The colloidal particles show much reduced photodynamic activity, low reactivity toward reducing agents, and low cytotoxicity. Accordingly, the colloidal MB was proposed and further investigated as a fluorescent particle tracer for the study of cell-nanoparticle interactions. In conclusion, MB can be efficiently and stably loaded into polysulfide organosilica colloidal particles using a simple and convenient physical route.
亚甲蓝（MB）是一种有着百年历史的药物和荧光染料，在药物治疗以及作为组织染色剂方面有着悠久且多样的应用历史。然而，MB在光照和还原剂存在的情况下本质上是不稳定的。在本研究中，我们旨在制备并表征基于多硫化物的有机硅胶体颗粒，用于高效、稳定且保护性地封装MB。含二硫化物和四硫化物的有机硅烷同系物被用作有机硅前驱体，基于二氧化硅茴香酒效应直接合成有机硅胶体。在颗粒形成过程中，MB自发地被包裹进胶体颗粒中。对胶体MB的以下性质进行了评估：粒径、表面电荷、原子分布、包封效率、MB释放、光动力活性、硫醇和抗坏血酸反应性以及细胞毒性。动态光散射测量表明，胶体MB的粒径可在100纳米至1微米范围内调节。扫描电子显微镜图像显示为球形颗粒，其粒径与组成有关，为70 - 120纳米（变异系数：15 - 18%）。MB以最高95%的效率被封装在胶体颗粒中。MB从胶体中的释放率在4小时时<1%，在48小时时<3.5%。胶体颗粒显示出大大降低的光动力活性、对还原剂的低反应性以及低细胞毒性。因此，提出并进一步研究了胶体MB作为用于研究细胞 - 纳米颗粒相互作用的荧光颗粒示踪剂。总之，使用简单便捷的物理方法可将MB高效且稳定地负载到多硫化物有机硅胶体颗粒中。
