Department of Pharmacology, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390, United States.
J Control Release. 2011 Dec 20;156(3):276-80. doi: 10.1016/j.jconrel.2011.08.019. Epub 2011 Aug 23.
Photodynamic therapy (PDT) is an emerging clinical modality for the treatment of a variety of diseases. Most photosensitizers are hydrophobic and poorly soluble in water. Many new nanoplatforms have been successfully established to improve the delivery efficiency of PS drugs. However, few reported studies have investigated how the carrier microenvironment may affect the photophysical properties of photosensitizer (PS) drugs and subsequently, their biological efficacy in killing malignant cells. In this study, we describe the modulation of type I and II photoactivation processes of the photosensitizer, 5,10,15,20-tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP), by the micelle core environment. Electron-rich poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) micelles increased photoactivations from type II to type I mechanisms, which significantly increased the generation of O(2)(-) through the electron transfer pathway over (1)O(2) production through energy transfer process. The PDPA micelles led to enhanced phototoxicity over the electron-deficient poly(D,L-lactide) control in multiple cancer cell lines under argon-saturated conditions. These data suggest that micelle carriers may not only improve the bioavailability of photosensitizer drugs, but also modulate photophysical properties for improved PDT efficacy.
光动力疗法（PDT）是一种新兴的临床治疗方法，可用于治疗多种疾病。大多数光敏剂都是疏水性的，在水中溶解度差。许多新的纳米平台已经成功建立，以提高 PS 药物的递送效率。然而，很少有报道研究探讨载体微环境如何影响光敏剂（PS）药物的光物理性质，以及随后对杀伤恶性细胞的生物学功效的影响。在本研究中，我们描述了光敏剂 5,10,15,20-四（间-羟苯基）卟啉（mTHPP）的 I 型和 II 型光激活过程的调制，由胶束核环境决定。富电子聚（2-（二异丙基氨基）乙基甲基丙烯酸酯）（PDPA）胶束增加了从 II 型到 I 型机制的光激活，这通过电子转移途径显著增加了 O(2)(-)的产生，而不是通过能量转移过程产生 1O(2)。在氩气饱和条件下，PDPA 胶束在多种癌细胞系中导致光毒性比电子缺乏的聚（D，L-丙交酯）对照物显著增强。这些数据表明，胶束载体不仅可以提高光敏剂药物的生物利用度，还可以调节光物理性质以提高 PDT 疗效。
