A mitochondrial-targeted prodrug for NIR imaging guided and synergetic NIR photodynamic-chemo cancer therapyElectronic supplementary information (ESI) available. See DOI: 10.1039/c7sc03454g

• Main Authors: Liu, Hong-Wen, Hu, Xiao-Xiao, Li, Ke, Liu, Yongchao, Rong, Qiming, Zhu, Longmin, Yuan, Lin, Qu, Feng-Li, Zhang, Xiao-Bing, Tan, Weihong
• Format: Journal Article
• Language: English
• Published: 23.10.2017
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/c7sc03454g

Nontoxic prodrugs, especially activated by tumor microenvironment, are urgently required for reducing the side effects of cancer therapy. And combination of chemo-photodynamic therapy prodrugs show effectively synergetic therapeutic efficiency, however, this goal has not been achieved in a single molecule. In this work, we developed a mitochondrial-targeted prodrug PNPS for near infrared (NIR) fluorescence imaging guided and synergetic chemo-photodynamic precise cancer therapy for the first time. PNPS contains a NIR photosensitizer ( NPS ) and an anticancer drug 5′-deoxy-5-fluorouridine (5′-DFUR). These two parts are linked and caged through a bisboronate group, displaying no fluorescence and very low cytotoxicity. In the presence of H 2 O 2 , the bisboronate group is broken, resulting in activation of NPS for NIR photodynamic therapy and activation of 5′-DFUR for chemotherapy. The activated NPS can also provide a NIR fluorescence signal for monitoring the release of activated drug. Taking advantage of the high H 2 O 2 concentration in cancer cells, PNPS exhibits higher cytotoxicity to cancer cells than normal cells, resulting in lower side effects. In addition, based on its mitochondrial-targeted ability, PNPS exhibits enhanced chemotherapy efficiency compare to free 5′-DFUR. It also demonstrated a remarkably improved and synergistic chemo-photodynamic therapeutic effect for cancer cells. Moreover, PNPS exhibits excellent tumor microenvironment-activated performance when intravenously injected into tumor-bearing nude mice, as demonstrated by in vivo fluorescence imaging. Thus, PNPS is a promising prodrug for cancer therapy based on its tumor microenvironment-activated drug release, synergistic therapeutic effect and "turn-on" NIR imaging guide. Nontoxic prodrugs, especially activated by tumor microenvironment, are urgently required for reducing the side effects of cancer therapy.