CD-PLLD co-delivering docetaxel and MMP-9 siRNA plasmid for nasopharyngeal carcinoma therapy in vivo

The co-delivery of a drug and a target gene has become a primary strategy in cancer therapy. Based on our previous study, a synthesized starshaped copolymer consisting of βcyclodextrin (CD) and a poly(Llysine) dendron (PLLD) was used to co-deliver docetaxel (DOC) and matrix metalloproteinase 9 (MMP9) small interfering RNA, via CDPLLD/DOC/MMP9 complexes, into mice implanted with HNE1 human nasopharyngeal carcinoma (NPC) tumor cells in vivo. Unlike the commonly used amphiphilic copolymer micelles, the obtained CD derivative may be used directly for a combined delivery of nucleic acid and hydrophobic DOC without a complicated micellization process. In vivo assays demonstrated that CDPLLD/DOC/MMP9 inhibited HNE1 tumor growth and decreased proliferating cell nuclear antigen expression levels, indicating a potential strategy for NPC therapy. In addition, the distribution of DOC and MMP9 was investigated; CDPLLD/DOC/MMP9 complexes were phagocytized in reticuloendothelial systems, including the liver and spleen, which requires further study. Furthermore, the complexes did not cross the bloodbrain barrier due to their large molecular size, suggesting they may be relatively safe. Additionally, the complexes mediated increased DOC concentrations with prolonged blood circulation and EGFP expression in HNE1 tumors. These results suggest the future potential application of CD-PLLD/DOC/MMP-9 for NPC therapy.