All-trans retinoic acid-incorporated nanoparticles of deoxycholic acid-conjugated dextran for treatment of CT26 colorectal carcinoma cells

Abstract

Young Il Jeong,1,* Kyu Don Chung,2,* Da Hye Kim,3 Yoon Hyuk Kim,4 Yeon Soo Lee,5 Ki Choon Choi31Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, South Korea; 2Department of Anesthesiology and Pain Medicine, Catholic University, Seoul, South Korea; 3Grassland and Forage Research Center, Rural Development Administration, Cheonan, South Korea; 4Department of Mechanical Engineering, Kyung Hee University, Seoul, South Korea; 5Department of Biomedical Engineering, Catholic University of Daegu, Daegu, South Korea*These authors equally contributed to this workPurpose: All-trans retinoic acid (RA)-incorporated nanoparticles were prepared using deoxycholic acid-conjugated dextran (DexDA). Anticancer activity of RA-incorporated DexDA nanoparticles were tested in vitro and in vivo.Methods: RA-incorporated nanoparticles were prepared by dialysis. Antiproliferative and anti-invasive potential of RA-incorporated nanoparticles were studied using CT26 colorectal carcinoma cells.Results: RA-incorporated nanoparticles have small particle sizes of around 70–300 nm and spherical shapes. The higher drug-feeding ratio and higher substitution degree of deoxycholic acid in the conjugates resulted in higher drug contents, lower loading efficiency, and larger particle size. RA release rate became slower at higher drug contents and higher substitution degree of deoxycholic acid in the DexDA conjugates. The antiproliferation activity, anti-invasive activity, and matrix metalloproteinase 2 expression of RA-incorporated nanoparticles against CT26 cells in vitro was similar to RA. However, RA-incorporated nanoparticles had superior antimetastatic activity in an animal pulmonary metastatic model of CT26 cells compared to RA itself.Conclusion: RA-incorporated nanoparticles showed similar anticancer activity in vitro and superior antimetastatic activity in vivo in a pulmonary metastatic model of CT26 cells. We suggest that RA-incorporated nanoparticles are promising vehicles for efficient delivery of RA.Keywords: nanoparticle, dextran, deoxycholic acid, retinoic acid, cancer cell invasion