Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 26, Issue 34, Pages 6257-6269Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201602541
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Funding
- National Natural Science Foundation of China [51233003, 21474077, 51533006]
- Fundamental Research Funds for the Central Universities [2014203020204, 2014203020201]
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A multifunctional prodrug, designated as TPP-L-GEM, is fabricated to realize image-guided in situ tumor photodynamic therapy (PDT) with red light activatable chemotherapy. Gemcitabine is conjugated with a fluorescent photosensitizer, meso-tetraphenylporphyrin (TPP), by a reactive oxygen species cleavable thioketal linker. Under the irradiation of low-energy red light, TPP can generate singlet oxygen and damage tumor cells by photodynamic therapy. Simultaneously, the thioketal linkage can be cleaved by singlet oxygen and result in a cascaded gemcitabine release, causing sustained cell damage by chemotherapy. With the combination of PDT and cascaded chemotherapy, TPP-L-GEM shows significant tumor therapeutic efficacy in vitro and in vivo. Furthermore, the inherent fluorescent property of TPP endows the TPP-L-GEM prodrug with noninvasive drug tracking capability, which is favorable for image-guided tumor therapy.
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