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A folate-targeted PEGylated cyclodextrin-based nanoformulation achieves co-delivery of docetaxel and siRNA for colorectal cancer
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Accepted Version
Appendix A - Supplementary Data
Date
2021-07-14
Authors
Zou, Yifang
Xiao, Fang
Song, Liu
Sun, Bingxue
Sun, Dandan
Chu, Di
Wang, Limei
Han, Shulan
Yu, Zhuo
O'Driscoll, Caitríona M.
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier B.V.
Published Version
Abstract
Docetaxel (DTX) is a chemotherapeutic agent used for a range of cancers, but it has little activity against colorectal cancer (CRC). However, combination therapy with other therapeutic agents is a potential strategy to enhance the efficacy of DTX in CRC treatment. The nuclear factor-κB (NF-κB) signaling pathway is implicated in a variety of malignancies (e.g., CRC), and the blockade of NF-κB may increase the sensitivity of cancer cells to chemotherapy. The application of small interference RNA (siRNA) to inhibit the translation of complementary mRNA has demonstrated the potential for cancer gene therapy. In this study, an amphiphilic cationic cyclodextrin (CD) nanoparticle modified with PEGylated folate (FA; a ligand to target folate receptor on CRC) has been developed for co-delivery of DTX and siRNA (against the RelA, a subunit of NF-κB) in the treatment of CRC. The resultant co-formulation (CD.DTX.siRelA.PEG-FA) achieved cell-specific uptake indicating the function of the folate targeting ligand. The CD.DTX.siRelA.PEG-FA nanoparticle enhanced the apoptotic effect of DTX with the downregulation of RelA expression, which significantly retarded the growth of CRC in mice, without causing significant toxicity. These results suggest that the FA-targeted PEGylated CD-based co-formulation provides a promising strategy for combining DTX and siRNA in treating CRC.
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Keywords
Colorectal cancer , Nanoparticle , Chemotherapy , Gene therapy , Combination therapy
Citation
Zou, Y., Xiao, F., Song, L., Sun, B., Sun, D., Chu, D., Wang, L., Han, S., Yu, Z., O'Driscoll, C. M. and Guo, J. (2021) 'A folate-targeted PEGylated cyclodextrin-based nanoformulation achieves co-delivery of docetaxel and siRNA for colorectal cancer', International Journal of Pharmaceutics, 606, 120888 (9pp). doi: 10.1016/j.ijpharm.2021.120888