Ultrasound-Enhanced Delivery of Doxorubicin-Loaded Nanodiamonds from Pullulan-all-trans-Retinal Nanoparticles for Effective Cancer Therapy

Nanodiamond as a drug carrier is of great significance in improving cancer therapy by overcoming chemoresistance. However, its clinical application is severely limited because of insufficient tumor vascular penetration. To address this limitation, pullulan-all-trans-retinal (pullulan-ATR) self-assembled nanoparticles were prepared as nanocarriers, which encapsulated doxorubicin-loaded nanodiamonds, to construct a core-shell structured coloading nanosystem. The obtained composite nanoparticles show a homogeneous size distribution with good dispersity and pH sensitivity. Furthermore, ultrasound was utilized to promote the intratumoral penetration of these nanoparticles. As a result, the intracellular retention of DOX was efficiently enhanced, and DOX in the tumor tissue reached 17.3% of the injected dosage. The antitumor effect of this combined strategy was remarkably improved in both the DOX-sensitive HepG2 and DOX-resistant HepG2/ADR tumor models in vivo. This new strategy might serve as a powerful method to address the limitation of nanodiamonds and provide innovative ideas for the application of nanoparticles in clinical cancer therapy.