School of Biological Engineering, Dalian Polytechnic University, Ganjingzi District, Dalian, 116034, PR China.
State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Rd., Hi-tech Zone, Dalian, 116024, PR China; Shenzhen Research Institute, Dalian University of Technology, Nanshan District, Shenzhen, 518057, PR China.
Biomaterials. 2021 Feb;269:120532. doi: 10.1016/j.biomaterials.2020.120532. Epub 2020 Nov 16.
Photodynamic therapy (PDT) has been demonstrated to be effective for cancer treatment. Design of photosensitizers (PS) featuring tumor targeting, long excitation wavelengths, and high singlet oxygen quantum yields (Φ(O)) is the crucial point of highly efficient PDT. However, it is especially difficult to integrate above features into one photosensitizer. Herein, we put forwards a PS J-aggregation method, simultaneously endowing PS with the ability of tumor targeting, the red-shift of spectra, and the increase of Φ(O). Cyanine PS 4-((E)-3-((E)-5-iodo-1,3,3-trimethylindolin-2-ylidene)prop-1-en-1-yl)-1-methylquinolin-1-ium iodide (IDMQ) is firstly designed and synthesized by us. IDMQ can form smart response-type J-aggregates under the control of negatively charge in microenvironments. In blood, IDMQ J-aggregates target tumor via "enhanced permeability and retention (EPR)" effect. Then the intracellular IDMQ J-aggregates assembled by RNA facilitate the red shift of absorption peak with deeper penetration, and compared to free state IDMQ, improve the Φ(O), resulting in the bathochromic shift of optimal PDT wavelength from 630 (free state IDMQ) to 700 nm (IDMQ J-aggregates). This intelligent J-aggregation method establishes a promising way for endowing photosensitizer with the ability of tumor-targeting and the synchronous improvement of PDT efficacy and further boosts the development of PDT.
光动力疗法（PDT）已被证明对癌症治疗有效。设计具有肿瘤靶向、长激发波长和高光敏剂（PS）单线态氧量子产率（Φ（O））的 PS 是高效 PDT 的关键。然而，将上述特征集成到一个 PS 中尤其困难。在此，我们提出了一种 PS J-聚集方法，同时赋予 PS 肿瘤靶向、光谱红移和Φ（O）增加的能力。我们首次设计并合成了菁 PS 4-（（E）-3-（（E）-5-碘-1,3,3-三甲基吲哚啉-2-亚基）丙-1-烯-1-基）-1-甲基喹啉-1-碘化物（IDMQ）。在微环境中带负电荷的控制下，IDMQ 可以形成智能响应型 J-聚集体。在血液中，IDMQ J-聚集体通过“增强渗透和保留（EPR）”效应靶向肿瘤。然后，RNA 组装的细胞内 IDMQ J-聚集体有助于吸收峰的红移，具有更深的穿透性，与游离状态的 IDMQ 相比，提高了Φ（O），导致最佳 PDT 波长从 630nm（游离状态 IDMQ）到 700nm（IDMQ J-聚集体）的红移。这种智能 J-聚集方法为赋予 PS 肿瘤靶向能力和同步提高 PDT 疗效建立了一种很有前途的方法，并进一步推动了 PDT 的发展。
