Riboflavin-modified lipo-polyplexes co-delivering CXCR4 siRNA and doxorubicin for treatment of highly metastatic cancer

doi:10.5246/jcps.2021.03.015

Abstract

Abstract:

SDF-1/CXCR4 has been recognized as one of the most relevant chemokine signaling pathways to cancer metastasis, and siRNA targeting CXCR4 may provide potential improvements to treat those highly metastatic cancers, especially when combined with chemotherapy. In the present study, we constructed riboflavin-modified lipo-polyplexes to co-deliver CXCR4 siRNA and doxorubicin for cancer therapy. Doxorubicin was covalently conjugated to polyethyleneimine (PEI) with acid-cleavable hydrazine bond, and the obtained acid-sensitive conjugate was efficiently condensed with siRNA to form polyplexes, which were further coated with riboflavin-tailed lipid-membrane to prepare the lipo-polyplexes conveniently. Utilizing the fact that tumor cells overexpress riboflavin receptors, the riboflavin modification effectively enhanced uptake of lipo-polyplexes by tumor cells in a receptor-mediated manner. The riboflavin-modified lipo-polyplexes co-delivering CXCR4 siRNA and doxorubicin effectively decreased viability and invasiveness of tumor cells in vitro, and inhibited primary tumor growth and tumor metastasis in vivo.

Key words: Riboflavin, Lipo-polyplexes, Co-delivery, SiRNA, Doxorubicin

Supporting:

Kaisen Li, Rudong Wang, Yiwei Peng, Dawen Dong, Xianrong Qi. Riboflavin-modified lipo-polyplexes co-delivering CXCR4 siRNA and doxorubicin for treatment of highly metastatic cancer[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(3): 189-205.

Figures/Tables 8

Table 1. Size and zeta potential of the lipo-polyplexes.

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