Preparation and cytotoxicity evaluation of folic acid-modified YF8-OA self-assembled lipid prodrug nanoparticles

AbstractThis study aimed to improve the use of YF8, a matrine derivative obtained through chemical transformation of matrine extracted from Sophora alopecuroides. YF8 has demonstrated improved cytotoxicity compared to matrine, but its hydrophobic nature hinders its application. To overcome this, the lipid prodrug YF8-OA was synthesized by linking oleic acid (OA) to YF8 through an ester bond. Although YF8-OA could self-assemble into unique nanostructures in water, it was not sufficiently stable. To enhance the stability of YF8-OA lipid prodrug nanoparticles (LPs), we employed the strategy of PEGylation using DSPE-mPEG2000 or DSPE-mPEG2000 conjugated with folic acid (FA). This resulted in the formation of uniform spherical nanoparticles with greatly improved stability and a maximum drug load capacity upto 58.63%. Cytotoxicity was evaluated in A549, HeLa, and HepG2 cell lines. The results showed that in HeLa cells, the IC50 value of YF8-OA/LPs with FA-modified PEGylation was significantly lower than that of YF8-OA/LPs modified by PEGylation alone. However, no significant enhancement was observed in A549 and HepG2 cells. In conclusion, the lipid prodrug YF8-OA can form nanoparticles in aqueous solution to address its poor water solubility. Modification with FA resulted in further enhanced cytotoxicity, providing a potential avenue for exerting the antitumor activity of matrine analogs.Keywords: Matrine derivative YF8lipid prodrug nanoparticles (LPs)folic aciddrug releasecytotoxicity Disclosure statementNo potential conflict of interest was reported by the author(s).Additional informationFundingThis work was supported by the local funding project for scientific and technological development under the guidance of central government (GuiKe ZY21195012) and the Guangxi Natural Science Foundation (2020GXNSFAA297178).