Abstract
In this study, a tumor-targeting poly(d, l-lactic-co-glycolic acid) (PLGA) loaded “off-on” fluorescent probe nanoparticle (PFN) delivery system was developed to evaluate the region of tumor by off-on fluorescence. The biodegradability of the nanosize PFN delivery system readily released the probe under tumor acidic conditions. The probe with good biocompatibility was used to monitor the intracellular glutathione (GSH) of cancer cells and selectively localize to mitochondria for tumor imaging. The incorporated tumor-targeting probe was based on the molecular photoinduced electron transfer (PET) mechanism preventing fluorescence (“off” state) and could be easily released under tumor acidic conditions. However, the released tumor-targeting fluorescence probe molecule was selective towards GSH with high selectivity and an ultra-sensitivity for the mitochondria of cancer cells and tissues significantly increasing the probe molecule fluorescence signal (“on” state). The tumor-targeting fluorescence probe showed sensitivity to GSH avoiding interference from cysteine and homocysteine. The PFNs could enable fluorescence-guided cancer imaging during cancer therapy. This work may expand the biological applications of PFNs as a diagnostic reagent, which will be beneficial for fundamental research in tumor imaging.
The tumor-bearing mice were injected intravenously through the tail with the PFNs; after injection, the PFNs can accumulate to tumor region via the EPR effect. The PFNs can prolong blood circulation time and easily degraded under tumor acidic conditions to release an off-on probe in tumor, and the probe can target glutathione of mitochondria, making probe fluorescence enhanced largely (“on” state).
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Funding
We acknowledge the financial support from the National Natural Science Foundation of China (Grant No. 81503038) and the Scientific and Technological Project of Henan Province of China (no. 52110131).
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Yao, H., Cao, L., Zhao, W. et al. An off-on fluorescence probe targeting mitochondria based on oxidation-reduction response for tumor cell and tissue imaging. J Nanopart Res 19, 349 (2017). https://doi.org/10.1007/s11051-017-4030-4
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DOI: https://doi.org/10.1007/s11051-017-4030-4