Imaging-guided drug delivery via in vivo copper-free clicked clusters of quantum dot and dual responsive self-assembled Doxorubicin nanoparticles
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Real-time imaging and targeted drug delivery has been lately combined to enhance the therapeutic efficacy in cancer therapy. In this study, we prepared clickable doxorubicin nanoparticles (Dox NP) for theragnostic purposes. Dox conjugated with 8arm-PEG via disulfide bonds to form self-assembled nanoparticles. Dox NP were bi-functionalized with DBCO moiety for clusters formation with azide-modified quantum dots (QD) through copper-free click reaction and MMP cleavable linkers conjugated with methoxy-PEG to protect the Dox NP in circulation. At the high level of MMP-2 enzyme in tumor site, the fluorescence of QD was first quenched by Dox due to the clustering of Dox NP and QD via click reaction. Dox was subsequently released by cleavage of disulfide bonds resulting in recovery of QD fluorescence. Due to the quenching and recovering fluorescence behavior, our Dox NP is supposed to be employed as a molecular sensor for targeting and releasing of anticancer agents at tumor site