Abstract
Inspired by the specificity of acid tumor microenvironment, we constructed a flexible charge-reversible near-infrared (NIR) fluorescence nanoprobe in response to tumor extracellular pH (pHe) for effective tumor-specific imaging. The nanoprobe consists of an NIR-emitted CuInS2/ZnS quantum dot (CIS/ZS QDs) core and a tailored lauric acid and 2,3-dimethylmaleic anhydride modified ε-polylysine (ε-PL-g-LA/DMA) shell, which provides not only a dense protective layer for the QDs but also the ability of pHe-induced positive charge-mediated endocytosis into tumor cells. The results showed that the QDs@ε-PL-g-LA/DMA nanoprobe with a uniform size of 40 nm had high chemical stability at pH 7.4 and excellent optical properties. Especially, it swiftly reversed its surface charge to positive in 20 min when exposed to pHe due to the cleavage of the β-carboxyl amide bond of ε-PL-g-LA/DMA. Moreover, the cell uptake of the pHe-sensitive QDs nanoprobe exposed at pH 6.8 into HeLa cells is much more significant than that at pH 7.4, which further verified the availability of the electrostatic adsorptive endocytosis facilitated targeting ability. The pHe-induced targeting imparted the QDs nanoprobe a broad targeting ability in a variety of solid tumors. Furthermore, as an effective alternative mechanism for tumor targeting, responsive charge reversion is also universally applicable to other cancer theranostics agent.
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