Co-Delivery of Lycorine and the p53 Gene by Mesoporous Silica Nanoparticles with Synergistic Pro-Apoptotic Effects Against Chronic Myelocytic Leukemia

Mesoporous Silica Nanoparticles (MSNs) loaded with lycorine were previously reported to induce apoptosis of prostate cancer cells with remarkably enhanced efficiency and reduced side effects. In the current study, MSNs-based co-delivery of lycorine and/or the tumor suppressor gene p53 was developed for drug delivery to chronic myelocytic leukemia (CML) cell line K562. We have demonstrated that the simultaneous delivery of lycorine and p53 via MSNs achieved synergistic anti-proliferative and pro-apoptotic effects on K562 cells when compared to MSNs loaded with lycorine only. The cell viability assay on K562 cells showed that the half-maximal inhibitory concentration (IC50) after 48 h of treatment with MSNs@Lycorine@pcDNA3.1-p53 was only 20% of that for MSNs@Lycorine. Furthermore, the Annexin V-FITC/PI assay for K562 cell apoptosis demonstrated a markedly higher apoptotic rate in the group treated with MSNs@Lycorine@pcDNA3.1-p53 when compared to that of the MSNs@Lycorine group; this result was consistent with the accumulation of the p53 protein. These findings indicate that MSNs could be an ideal nanovector for simultaneous delivery of drugs and genes for improved cancer therapy and that an MSN-based lycorine/wt-p53 co-delivery system with efficient endocytosis, sustained drug-releasing property, excellent biocompatibility, and enhanced synergistic proapoptotic effects might be a new promising strategy for the treatment of CML.