Kirla Haritha, Wu Jiansha, Hamzah Juliana, Henry David J
Chemistry and Physics, College of Science, Technology, Engineering and Maths, Murdoch University, WA 6150, Australia; Targeted Drug Delivery, Imaging & Therapy Laboratory, Harry Perkins Institute of Medical Research, The University of Western Australia, Centre for Medical Research, Nedlands, WA 6009, Australia.
Chemistry and Physics, College of Science, Technology, Engineering and Maths, Murdoch University, WA 6150, Australia; Targeted Drug Delivery, Imaging & Therapy Laboratory, Harry Perkins Institute of Medical Research, The University of Western Australia, Centre for Medical Research, Nedlands, WA 6009, Australia.
Colloids Surf B Biointerfaces. 2025 Jan;245:114195. doi: 10.1016/j.colsurfb.2024.114195. Epub 2024 Aug 30.
Photodynamic therapy (PDT) is an emerging clinical modality for diverse disease conditions, including cancer. This technique involves, the generation of cytotoxic reactive oxygen species by a photosensitizer in the presence of light and oxygen. Methylene blue (MB) is a cationic dye with an ability to act as photosensitizing and bioimaging agent. The direct utilization of MB as photosensitizer for biological applications has often been impeded by its poor photostability and unwanted tissue interactions. Nanocarriers such as mesoporous silica nanoparticles (MSNs) provide an effective means of overcoming these limitations. However, the mere physical adsorption of the dye within the MSN can result in leakage, compromising the effectiveness of PDT. Therefore, in this work, we report the conjugation of MB into MSNs using novel MB-silane derivatives, namely MBS1 and MBS2, to create dye-doped and amine-functionalized MSNs (MBS1-AMSN and MBS2-AMSN). The PDT efficacy and bioimaging capability of these nanoparticles were compared with those of MSNs in which MB was non-covalently encapsulated (MB@AMSN). The synthesized nanoparticles, ultra-small in size (≤ 35 ± 4 nm) with monodispersity, exhibited enhanced fluorescence quantum yields. MBS1-AMSN demonstrated 70-fold increase, while MBS2-AMSN showed 33-fold improvement in fluorescence quantum yields compared to MB@AMSN at the same concentration. Covalent conjugation resulted in a 2-fold enhancement in the singlet oxygen quantum yield of the dye in MBS1-AMSN and 1.2-fold improvement in MBS2-AMSN, compared to non-covalent encapsulation. Assessment on RAW 264.7 macrophages revealed superior fluorescence in cell imaging for MBS1-AMSN, establishing it as a more efficient PDT agent compared to MBS2-AMSN and MB@AMSN. These findings suggest that MBS1-AMSN holds significant potential as a theranostic nanoplatform for image-guided PDT.
光动力疗法（PDT）是一种用于多种疾病（包括癌症）的新兴临床治疗方法。该技术涉及在光和氧存在的情况下，由光敏剂产生活性氧细胞毒素。亚甲蓝（MB）是一种阳离子染料，具有作为光敏剂和生物成像剂的能力。MB作为生物应用的光敏剂的直接利用常常因其光稳定性差和不必要的组织相互作用而受到阻碍。纳米载体如介孔二氧化硅纳米颗粒（MSNs）提供了克服这些限制的有效手段。然而，染料在MSN内的单纯物理吸附可能导致泄漏，从而影响PDT的有效性。因此，在这项工作中，我们报告了使用新型MB-硅烷衍生物（即MBS1和MBS2）将MB共轭到MSNs中，以制备染料掺杂和胺功能化的MSNs（MBS1-AMSN和MBS2-AMSN）。将这些纳米颗粒的PDT疗效和生物成像能力与MB非共价封装的MSNs（MB@AMSN）进行了比较。合成的纳米颗粒尺寸超小（≤35±4nm）且具有单分散性，表现出增强的荧光量子产率。与相同浓度下的MB@AMSN相比，MBS1-AMSN的荧光量子产率提高了70倍，而MBS2-AMSN提高了33倍。与非共价封装相比，共价共轭使MBS1-AMSN中染料的单线态氧量子产率提高了2倍，MBS2-AMSN提高了1.2倍。对RAW 264.7巨噬细胞的评估显示，MBS1-AMSN在细胞成像中具有优异的荧光，使其成为比MBS2-AMSN和MB@AMSN更有效的PDT剂。这些发现表明，MBS1-AMSN作为用于图像引导PDT的治疗诊断纳米平台具有巨大潜力。
