Hyaluronic acid-exposed nanoparticles delivered raloxifene against colon cancerous cells and orcasterated epigenetics

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Abstract Colorectal cancer (CRC) is one of the world's mortality causes. Despite recent breakthroughs in treatment, the prognosis for CRC remains poor due to drug resistance. Raloxifene (RX) was recently licensed for the prevention of CRC. We proposed a unique delivery approach to improve the activity of RX by combining with hyaluronic acid (HA) and chitosan (CS). Consequently, we explored the cytotoxic and epigenetic effects of RX-HA-CS nanoparticles (RX NPs) against Caco-2 and HCT 116 cell lines. The entrapment efficiency (EE%) of RX in its NP was 90.0 ± 8.12%. In addition, RX NPs induced higher cytotoxic effect against Caco-2 cells than HCT 116 cells. The cytotoxic fold changes of the RX NP in Caco-2 and HCT 116 cells were 2.52 and 2.16, respectively, compared with the free counterpart. The epigenetic mechanistic effects of these proposed regimens on non-coding-RNAs were investigated. Additionally, some protein levels were assessed in CRC cells upon treatments. Intriguingly, it was suggested that RX NPs tackled the CRC cells through down-regulation of H-19, HOTTIP, HULC, LINC00641, miR-200, miR-92a, miR-21, YKL-40, PPARγ, and VEGF, as well as up-regulation of miR-944 and ECN. We can conclude that the RX NP promisingly tackles CRC cells through modulations of lncRNAs and miRNAs.

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