Synthesis of hyaluronic acid-grafted hollow mesoporous silica nanoparticles as nano-carriers for anticancer drug delivery

In this study, hyaluronic acid-functionalized disulfide hollow mesoporous silica nanoparticles (HMSN-NH2-HA) were synthesized as an anticancer drug delivery system. In this regard, hyaluronic acid, a natural ligand for cluster of differentiation-44 (CD44) receptors overexpressed on the surface of tumor cells, was covalently grafted onto the HMSNs. The nanoparticles were characterized using various techniques, such as transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FTIR). Doxorubicin hydrochloride (DOX) was loaded into HMSN-NH2-HA as a model medication. The in vitro drug release was evaluated in different medium conditions and was analyzed by high-performance liquid chromatography. Cellular viability and the localization of nanoparticles were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and confocal microscopy. The in vivo release of DOX in BALB/c mice was investigated by ex vivo images obtained by fluorescence microscopy. The TEM images of HMSNs revealed hollow spheres with an average size of approximately 150 nm. After grafting the HMSNs with hyaluronic acid, the hydrodynamic size of nanoparticles increased to 197 nm, and the zeta potential changed from − 40 to − 18 mV. The half inhibitory concentration (IC50) of HMSN-NH2-HA@DOX and HMSN@DOX for MDA-MB-231 cells after 48 h was 0.32 and 0.21 µg/ml, respectively. Ex vivo biodistribution analysis showed that the tumor-to-nontumor ratio was higher in the HMSN-NH2-HA@DOX group compared to the DOX group. This nanoparticle could provide new opportunities for DOX tumor delivery owing to its biodegradability, controlled release, and targeting behavior.Graphical abstract