期刊
ADVANCED FUNCTIONAL MATERIALS
卷 26, 期 41, 页码 7431-7442出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201602963
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资金
- National Basic Research Program of China [2013CB932704]
- National Natural Science Foundation of China [81521005, 21305047, 31622025]
- Youth Innovation Promotion Association CAS [2014248]
Integration of chemotherapy with photodynamic therapy (PDT) has been emerging as a novel strategy for treatment of triple negative breast cancer (TNBC). However, the clinical translation of this approach is hindered by the unwanted dark toxicity due to the always-on model and low tumor specificity of currently approved photosensitizer (PS). Here, the design of a multifunctional prodrug nanoparticle (NP) is described for precise imaging and organelle-specific combination cancer therapy. The prodrug NP is composed of a newly synthesized oxaliplatin prodrug, hexadecyl-oxaliplatintrimethyleneamine (HOT), an acid-activatable PS, derivative of Chlorin e6 (AC), and functionalized with a targeting ligand iRGD for tumor homing and penetration. HOT displays much higher antitumor efficiency than oxaliplatin by simultaneously inducing mitochondria depolarizing and DNA cross-linking. AC is specifically activated in the orthotopic or metastatic TNBC tumor for fluorescence imaging and PDT, while it remains inert in blood circulation to minimize the dark toxicity. Under the guide of acid-activatable fluorescence imaging, PDT and chemotherapy can be synergistically performed for highly efficient regression of TNBC. Taken together, this versatile prodrug nanoplatform could achieve tumor-specific imaging and organelle-specific combination therapy, which can provide an alternative option for cancer theranostic.
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