Journal
NANOSCALE
Volume 10, Issue 22, Pages 10514-10527Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c8nr02534g
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Funding
- National Basic Research Program of China [2015CB931802]
- National Science Foundation of China [81627901, 81473171, 81573013, 31700867]
- PCSIRT [IRT13016]
- Scientific Research Foundation of Huazhong University of Science and Technology [3004170130]
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Herein, reduction-responsive disintegratable nanoclusters (NCs) were prepared as a novel nanovehicle for targeted drug delivery. The NCs, with a diameter of similar to 170 nm, were self-assembled from hydrophobically modified and iRGD decorated hydroxyethyl starch (iRGD-HES-SS-C18). DOX was loaded into the NCs as a model drug. DOX@iRGD-HES-SS-C18 NCs can disintegrate into smaller ones and release DOX under reduction stimuli. Due to the ligand-receptor binding interactions between iRGD and integrin alpha V, DOX@iRGD-HES-SS-C18 NCs can specifically bind to the cell membranes of HepG-2 and 4T1 cells (integrin alpha V positive), resulting in enhanced cellular uptake as compared to DOX@HES-SS-C18 NCs. After cellular internalization, the NCs were transported to endosomes/lysosomes in which the reductive environment triggered the disintegration and DOX release. As a consequence, DOX@iRGD-HES-SS-C18 NCs exhibited an enhanced antitumor effect as compared to DOX@HES-SS-C18 NCs and free DOX, in an in vitro antitumor activity study. The reduction-responsive disintegratable NCs reported here were proved to be a safe and efficient nanoplatform, holding significant translation potential for tumor-targeted drug delivery.
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