pH-Sensitive N-doped carbon dots–heparin and doxorubicin drug delivery system: preparation and anticancer research

Abstract

In this study, doxorubicin (DOX) hydrochloride as a model drug, N-doped carbon dots as a drug carrier, and heparin as an auxiliary medicine were selected to design and prepare a multi-functional drug delivery system with pH-triggered drug release. The CDs were anchored onto heparin via chemical bonds and DOX was then loaded on CDs–Hep by taking advantage of the electrostatic interactions between DOX and CDs–Hep. The structures of all the intermediates and final products were characterized and confirmed by ¹H NMR and FT-IR spectroscopies. The CDs–Hep/DOX drug delivery system exhibited good stability. However, in acidic buffer, Hep and DOX release rate was accelerated and it was pH-responsive. In vitro and in vivo studies confirmed the high biocompatibility and low-toxicity of the CDs. An MTT assay showed that inhibition rate of CDs–Hep/DOX for HeLa, MCF-7 and A549 cells was close to that of DOX, indicating that the prepared drug system has a higher toxicity for tumor cells and can achieve an effective therapeutic effect. This systemic evaluation suggests that the introduction of Hep improves blood compatibility. In addition, the internalization of CDs–Hep/DOX by A549 cells was further confirmed using laser scanning confocal microscopy. As a result, a therapy was achieved due to the incorporation of Hep and DOX.