Nanodiamonds (
NDs) as drug delivery vehicles are of great significance in anticancer
therapy through enhancing drug retention. However, the major barrier to clinical application of
NDs is insufficient
tumor penetration owing to their strong aggregation and low passive penetration efficiency. Herein, the core-crosslinked
pullulan carrier, assembled using the visible light-induced diselenide (Se-Se) bond crosslinking method for encapsulating
nanodiamonds-
doxorubicin (NDX), is proposed to improve monodispersity. Furthermore, the core-crosslinked diselenide bond provides the nanosystem with redox-responsive capability and improved structural stability in a physiological environment, which prevents premature drug leakage and achieves
tumor site-specific controlled release. What's more, ultrasound (US) is utilized to promote nanosystem intratumoral penetration via enlarged
tumor vascular endothelium cell gaps. As expected, the nanosystem combined with ultrasound can enhance anti-
tumor efficacy with deep penetration and excellent retention performance in a HepG2 xenograft mouse model. This study highlights the ability of the integrated therapeutic paradigm to overcome the limitation of
nanodiamonds and the potential for further application in
cancer therapy.