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J Am Chem Soc. 2014 Apr 16;136(15):5647-55. doi: 10.1021/ja4108287. Epub 2014 Apr 1.

Multifunctional tumor pH-sensitive self-assembled nanoparticles for bimodal imaging and treatment of resistant heterogeneous tumors.

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1
Center for Nanoparticle Research, Institute for Basic Science (IBS) , Seoul 151-742, Korea.

Abstract

Nanoparticle-based diagnosis-therapy integrative systems represent an emerging approach to cancer treatment. However, the diagnostic sensitivity, treatment efficacy, and bioavailability of nanoparticles as well as the heterogeneity and drug resistance of tumors pose tremendous challenges for clinical implementation. We herein report on the fabrication of tumor pH-sensitive magnetic nanogrenades (termed PMNs) composed of self-assembled iron oxide nanoparticles and pH-responsive ligands. These PMNs can readily target tumors via surface-charge switching triggered by the acidic tumor microenvironment, and are further disassembled into a highly active state in acidic subcellular compartments that "turns on" MR contrast, fluorescence and photodynamic therapeutic activity. We successfully visualized small tumors implanted in mice via unique pH-responsive T1MR contrast and fluorescence, demonstrating early stage diagnosis of tumors without using any targeting agents. Furthermore, pH-triggered generation of singlet oxygen enabled pH-dependent photodynamic therapy to selectively kill cancer cells. In particular, we demonstrated the superior therapeutic efficacy of PMNs in highly heterogeneous drug-resistant tumors, showing a great potential for clinical applications.

PMID:
24689550
DOI:
10.1021/ja4108287
[Indexed for MEDLINE]
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