Intracellular "activated" two-photon photodynamic therapy by fluorescent conveyor and photosensitizer co-encapsulating pH-responsive micelles against breast cancer

• Published in: International journal of nanomedicine Vol. 12; pp. 5189 - 5201
• Main Authors: Luo, Lei, Zhong, Hong, Liu, Shuang, Deng, Lidong, Luo, Yonghuang, Zhang, Qiong, Zhu, Yingzhong, Tian, Yupeng, Sun, Yuan, Tian, Xiaohe
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2017; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Animals; Antigens; Biochemistry; Breast cancer; Breast Neoplasms - drug therapy; Cancer therapies; cancer therapy; Care and treatment; Cell Line, Tumor; Chlorophyll - analogs & derivatives; Chlorophyll - chemistry; Chlorophyll - pharmacokinetics; Chlorophyll - pharmacology; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug delivery systems; Female; Humans; Hydrogen-Ion Concentration; Light; Mice, Inbred BALB C; Micelles; Morphology; Nanoparticles; Original Research; pH responsiveness; Photochemotherapy; Photochemotherapy - methods; Photodynamic therapy; Photons; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - pharmacology; Physiological aspects; Polymers; Polymers - chemistry; Properties; Reactive Oxygen Species - metabolism; Scanning electron microscopy; Silicon wafers; Tissue Distribution; two-photon absorbance; Xenograft Model Antitumor Assays; United States; China; Japan; cancer therapy; pH responsiveness; two-photon absorbance; drug delivery; photodynamic therapy
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S140345

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.