International Journal of Nanomedicine (Jul 2017)
Intracellular “activated” two-photon photodynamic therapy by fluorescent conveyor and photosensitizer co-encapsulating pH-responsive micelles against breast cancer
Abstract
Lei Luo,1 Hong Zhong,1 Shuang Liu,1 Lidong Deng,1 Yonghuang Luo,1 Qiong Zhang,2 Yingzhong Zhu,2 Yupeng Tian,2 Yuan Sun,3 Xiaohe Tian4 1College of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of China; 2Department of Chemistry, Key Laboratory of Functional Inorganic Material Chemistry of Anhui Province, Anhui University, Hefei, People’s Republic of China; 3Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA; 4School of Life Science, Anhui University, Hefei, People’s Republic of China Abstract: The application of photodynamic therapy (PDT) for the diagnosis and treatment of cancer is hindered by the intrinsic defects of the currently available photosensitizers (PSs), such as poor water solubility and limited light-penetration depth. In this study, pH-responsive polymeric micelles that co-encapsulate therapeutic PSs and organooxotin two-photon compounds were applied for two-photon PDT (TP-PDT) against breast cancer. The TP-PDT effect of the drug-loaded micelles was “activated” when the micelles turned into aggregates at a triggering pH level. The in vitro therapeutic effect was evaluated on 4T1 murine breast cancer cells by viability assays, real-time morphology collapsing, and reactive oxygen species determination. Time-dependent ex vivo organ distribution and in vivo anticancer efficacy results suggested that the drug carriers could accumulate in tumors and suppress tumor growth by TP-PDT. The delivery system could enhance the solubility and distribution of PSs and, if administered along with a tissue-penetrating prolonged light source, could thus have good potential for cancer therapy. Keywords: photodynamic therapy, two-photon absorbance, drug delivery, pH responsiveness, cancer therapy
