pH-Sensitive ZnO Quantum Dots–Doxorubicin Nanoparticles for Lung Cancer Targeted Drug Delivery

TLDR

The study presents a ZnO quantum dot platform that delivers doxorubicin in a pH‑responsive manner for controlled intracellular release. Acid‑decomposable, luminescent aminated ZnO QDs (~3 nm) were synthesized, PEGylated for stability, conjugated with hyaluronic acid for CD44 targeting, loaded with doxorubicin via metal–drug complexes, and release DOX upon ZnO dissolution in acidic endosomes. The platform produced synergistic antitumor activity from combined Zn²⁺ and doxorubicin release.

Abstract

In this paper, we reported a ZnO quantum dots-based pH-responsive drug delivery platform for intracellular controlled release of drugs. Acid-decomposable, luminescent aminated ZnO quantum dots (QDs) were synthesized as nanocarriers with ultrasmall size (∼3 nm). The dicarboxyl-terminated poly(ethylene glycol) (PEG) had been introduced to NH2–ZnO QDs, which rendered it stable under physiological fluid. Moreover, a targeting ligand, hyaluronic acid (HA), was conjugated to ZnO QDs for specifically binding to the overexpressed glycoprotein CD44 by cancer cells. Doxorubicin (DOX) molecules were successfully loaded to PEG functionalized ZnO QDs via formation of metal–DOX complex and covalent interactions. The pH-sensitive ZnO QDs dissolved to Zn2+ in acidic endosome/lysosome after uptake by cancer cells, which triggered dissociation of the metal–drug complex and a controlled DOX release. As result, a synergistic therapy was achieved due to incorporation of the antitumor effect of Zn2+ and DOX.