Construction and performance evaluation of pH-responsive oxidized hyaluronic acid hollow mesoporous silica nanoparticles

In this study, hollow mesoporous silica (HMSN) was created to facilitate drug distribution using the hard template method. The oxidized hyaluronic acid (oxiHA) was coated on the carrier surface by the Schiff base reaction, producing the pH-responsive nanoparticles HMSNs-DOX-oxiHA targeted by CD44 and preventing drug leakage from mesopores. The prepared nanoparticles had a size of 151.79 ± 13.52 nm and a surface potential of −8.42 ± 0.48 mV. The rich mesoporous structure and internal cavity of HMSNs-NH2 achieved the effective encapsulation and loading rates of doxorubicin (DOX) at 76.84 ± 0.24 % and 18.73 ± 0.05 %, respectively. Owing to the pH sensitivity of imine bonds, HMSNs-DOX-oxiHA has a good pH response and release performance. The in vitro experiments showed that the nanoparticles were not cytotoxic and could enhance HCT-116 uptake efficiency by hyaluronic acid/CD44 receptor-mediated endocytosis, effectively inhibiting tumor cell proliferation and reducing toxic side effects on normal cells. In summary, the polysaccharide-based nano-drug delivery system constructed in this experiment not only has the basic response properties of a carrier but also introduces the bioactive advantages of natural polysaccharides.