Targeted delivery of 5-fluorouracil, miR-532-3p, and si-KRAS to the colorectal tumor using layer-by-layer liposomes

Maryamsadat Shahidi; Omid Abazari; Parisa Dayati; Bibi Fatemeh Haghiralsadat; Fatemeh Oroojalian; Davood Tofighi

doi:10.3389/fbioe.2022.1013541

Targeted delivery of 5-fluorouracil, miR-532-3p, and si-KRAS to the colorectal tumor using layer-by-layer liposomes

Front Bioeng Biotechnol. 2022 Oct 17:10:1013541. doi: 10.3389/fbioe.2022.1013541. eCollection 2022.

Authors

Maryamsadat Shahidi¹, Omid Abazari¹, Parisa Dayati², Bibi Fatemeh Haghiralsadat³, Fatemeh Oroojalian^{4

5}, Davood Tofighi⁶

Affiliations

¹ Department of Clinical Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
² Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
³ Medical Nanotechnology and Tissue Engineering Research Center, Yazd Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
⁴ Department of Advanced Technologies, School of Medicine, North Khorasan University of Medical Sciences, Bojnūrd, Iran.
⁵ Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran.
⁶ Department of Psychology, University of New Mexico, Albuquerque, NM, United States.

Abstract

Co-delivery of siRNA or miRNA with chemotherapeutic drugs into tumor sites is an attractive synergetic strategy for treating colorectal cancer (CRC) due to their complementary mechanisms. In the current work, a liposome nanoparticle (Huang et al., Cancer Metastasis Rev., 2018, 37, 173-187) coated by cationic chitosan (CS) using a controlled layer-by-layer (LbL) process was designed to deliver simultaneous si-KRAS, miRNA-532-3p, and 5-Fluorouracil (5-FU) into CRC cells. The LbL NPs exhibited a spherical structure with an average size of 165.9 nm and effectively protected si-KRAS and miRNA-532-3p against degradation by serum and nucleases. Interestingly, the LbL NPs were successfully entered into cells and efficiently promoted cytotoxicity and suppressed cancer cell migration and invasion. In vivo, the LbL NPs reduced tumor growth in SW480-tumor-bearing mice models. In conclusion, these results suggested that the LbL NPs co-loaded with 5-FU and miR-532-3p/si-KRAS might provide a promising potential strategy for inhibiting the malignant phenotypes of CRC cells.

Keywords: 5-fluorouracil; MiR-532-3p; colorectal cancer; liposome; si-KRAS.