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

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 H-1 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.