Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea; Department of Chemical and Biological Engineering, Korea University, 5-1 Anam-dong, Seongbuk-gu, Seoul 136-701, South Korea.
Center for Theragnosis, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul 136-791, South Korea.
J Control Release. 2015 Jul 10;209:12-9. doi: 10.1016/j.jconrel.2015.04.011. Epub 2015 Apr 12.
Methylene blue (MB), a water-soluble cationic dye widely used in the clinic, is known to photosensitize the generation of cytotoxic singlet oxygen efficiently, and thus, has attracted interest as a potential drug for photodynamic therapy (PDT). However, its use for the in vivo PDT of cancer has been limited due to the inherently poor cell/tissue accumulation and low biological stability in the free molecular form. Here, we report a simple and biocompatible nanocomplex formulation of MB (NanoMB) that is useful for in vivo locoregional cancer treatment by PDT. NanoMB particles were constructed through the self-assembly of clinically usable molecules (MB, fatty acid and a clinically approved polymer surfactant) directed by the dual (electrostatic and hydrophobic) interactions between the ternary constituents. The nanocomplexed MB showed greatly enhanced cell internalization while keeping the photosensitization efficiency as high as free MB, leading to distinctive phototoxicity toward cancer cells. When administered to human breast cancer xenograft mice by peritumoral injection, NanoMB was capable of facile penetration into the tumor followed by cancer cell accumulation, as examined in vivo and histologically with the near-infrared fluorescence signal of MB. The quintuple PDT treatment by a combination of peritumorally injected NanoMB and selective laser irradiation suppressed the tumor volume efficaciously, demonstrating potential of NanoMB-based PDT as a biocompatible and safe method for adjuvant locoregional cancer treatment.
亚甲蓝（MB）是一种水溶性阳离子染料，广泛应用于临床，已知可有效地光敏化产生细胞毒性单线态氧，因此作为光动力疗法（PDT）的潜在药物引起了人们的兴趣。然而，由于其在游离分子形式下内在的细胞/组织积累差和生物稳定性低，其在体内癌症 PDT 中的应用受到限制。在这里，我们报告了一种 MB（NanoMB）的简单且生物相容的纳米复合物制剂，通过 PDT 对体内局部癌症治疗有用。NanoMB 颗粒是通过临床可用分子（MB、脂肪酸和临床批准的聚合物表面活性剂）在三元成分之间的双重（静电和疏水）相互作用的指导下自组装构建的。纳米复合物化的 MB 表现出大大增强的细胞内化，同时保持与游离 MB 一样高的光敏化效率，导致对癌细胞具有独特的光毒性。当通过瘤周注射施用于人乳腺癌异种移植小鼠时，NanoMB 能够轻易地穿透肿瘤，然后积聚癌细胞，如体内和组织学检查中 MB 的近红外荧光信号所示。通过瘤周注射的 NanoMB 和选择性激光照射的组合进行五次 PDT 治疗，有效地抑制了肿瘤体积，表明基于 NanoMB 的 PDT 作为辅助局部癌症治疗的生物相容和安全方法具有潜力。
