Synthesis, characterization, and application of self-assembled safflower polysaccharide nanoparticles as liver targeting drug delivery carrier

Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death with chemotherapy and traditional surgery showing limited effectiveness. The present work aimed to study the feasibility of safflower polysaccharide (SPS) as an instinctive liver-targeting drug delivery carrier with applications in HCC. SPS-polyethyleneimine (SPS-PEI), hyaluronic acid-SPS-polyethyleneimine (HA-SPS-PEI), and hyaluronic acid-folic acid-SPS-polyethyleneimine (HA-FA-SPS-PEI) conjugates were synthesized by an esterification reaction and characterized by conventional methods. SPS-PEI, HA-SPS-PEI, and HA-FA-SPS-PEI self-assembled nanoparticles (SPNPs, HSPNPs, and HFSPNPs, respectively) and siRNA-loaded SPNPs, HSPNPs, and HASPNPs (siRNA ^FAM /SPNPs, siRNA ^FAM /HSPNPs and siRNA/HASPNPs, respectively) were fabricated with a roughly spherical shape, with sizes were ranging 100 ~ 200 nm in aqueous solution. Compared with free siRNA ^FAM , siRNA ^FAM /HASPNPs displayed enhanced serum stability, hypo toxicity, and a sustained release of siRNA ^FAM over 64 h. In the in vivo cellular uptake behavior study, the HASPNPs showed excellent HCC tumor-targeting capability because of the specific recognition by the folic acid and hyaluronan receptors (CD44) overexpressed on the HCC tumor membrane. The tissue staining of siRNA ^FAM /HASPNPs in mice further demonstrated that HASPNPs could distinctly enhance the distribution of siRNA ^FAM into the HCC tumor. Our results indicate that HASPNPs may serve as a promising HCC tumor-targeting drug delivery carrier for HCC prevention.