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.