Enhancing hemocompatibility and the performance of Au@silica nanoparticles by coating with cRGD functionalized zein

Poor safety and effectiveness is an outstanding challenge in the preparation of drug delivery systems (DDS) for cancer treatment. The pursuit of the high curative effect will inevitably increase the risk of adverse side effects. Herein, a bio-safe DDS was constructed by combining the advantages of functional zein and Au doped mesoporous silica nanoparticles (Au@SiO₂) to achieve chemo-photothermal therapy. The cRGD functionalized zein (cRGD-Zein) was coated on the surface of Au@SiO₂ which effectively avoided premature leakage of paclitaxel and realized sustained drug release. Meanwhile, the high hemolysis rate (107%) of Au@SiO₂ had been significantly reduced to 4%. The anti-hemolysis mechanism of functionalized zein was explored to give a deeper understanding of the interaction between nanoparticles and RBCs. The results showed that the functional zein would change the protein conformation during the interaction with Au@SiO₂ to protect the RBCs from the damage of Au@SiO₂. And the release rate of hemoglobin was limited by the size of RBCs membrane cracks with approximately 40 nm in width and 470 nm in length. The cell cytotoxicity and uptake assays showed that the prepared DDS exhibited low tumour cell viability (35%) and enhanced uptake performance (99.3%). This work suggested that the prepared nanoparticles could serve as a promising carrier to achieve safe and efficacious tumour therapy.