State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing 210093, China.
State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, Nanjing 210093, China; Institute of Drug R&D, Medical School of Nanjing University, Nanjing 210093, China; Jiangsu R&D Platform for Controlled & Targeted Drug Delivery, Nanjing University, Nanjing 210093, China; Jiangsu Key Laboratory for Nano Technology, Nanjing University, Nanjing 210093, China.
Biomaterials. 2016 Nov;107:23-32. doi: 10.1016/j.biomaterials.2016.08.037. Epub 2016 Aug 24.
Photodynamic therapy (PDT) is the combination of light and photosensitizer (PS) to kill tumor cells, which has the potential to meet many currently unmet medical needs. However, the whole body distribution and activatability by sunlight of photosensitizers to induce skin photosensitivity have limited the extensive clinic application of PDT. Herein, a novel strategy is presented to overcome these limitations by using a hydrophobic Near-infared (NIR) dye IR-780 iodide (IR780) to induce the self-assembly of albumin-PS conjugates, as a switchable PDT (Switch-PDT) agent. The PDT effect of PS is effectively inhibited by IR780 and recovered by NIR light irradiation in vitro. This quench/recovery strategy dose not sacrifice the anti-tumor ability in vivo, and the combined PDT and PTT (photothermal) effect contributes a very effective tumor inhibition rate of 100%. More importantly, the PDT effect is significantly suppressed after intravenous administration in mice or subcutaneous administration in rabbits as exhibited by the negligible skin response, while traditional PDT agent arouses severe skin erythema and edema. To the best of our knowledge, the switchable PDT is the first time to be used to eradicate the skin photosensitization of PS in vivo.
光动力疗法（PDT）是将光与光敏剂（PS）结合来杀死肿瘤细胞，它有潜力满足许多目前尚未满足的医疗需求。然而，PS 的全身分布和对阳光的激活能力会引起皮肤光敏性，限制了 PDT 的广泛临床应用。在此，提出了一种新策略，通过使用疏水性近红外（NIR）染料 IR-780 碘化物（IR780）诱导白蛋白-PS 缀合物的自组装，作为一种可切换的 PDT（Switch-PDT）剂来克服这些限制。PS 的 PDT 效应可通过 IR780 有效抑制，并可通过近红外光照射在体外恢复。这种猝灭/恢复策略不会牺牲体内的抗肿瘤能力，并且 PDT 和 PTT（光热）联合效应导致 100%的非常有效的肿瘤抑制率。更重要的是，与传统 PDT 剂引起严重的皮肤红斑和水肿相比，静脉注射给药后或皮下给药后在小鼠或兔子中观察到 PDT 效应显著抑制，几乎没有皮肤反应。据我们所知，可切换的 PDT 是首次用于消除体内 PS 的皮肤光敏性。
