Fabrication of paclitaxel loaded PLA/PCN-224 metal-organic framework for targeted high-intensity focused ultrasound driven sonodynamic therapy on hypoxia alleviated liver cancer cells.

High-intensity focused ultrasound (HIFU) is an effective, non-invasive ablative therapy, but incomplete tumor ablation often leads to recurrence and progression. To address this issue, the alternative promising therapy of HIFU combined with sonodynamic therapy enhances tumor ablation and reduces recurrence. Besides, the developing biocompatible and effective cancer therapy remains a significant issue. Herein, this study develop novel fabrication of paclitaxel (PLX) loaded poly lactic acid (PLA) with metal-organic framework (MOF: PCN-224) for targeted HIFU driven sonodynamic therapy on hypoxia alleviated HEP-G2 liver cancer cells. In in vitro drug release of PLX@PLA-PCN-224 in PBS exposure with 2 min of 1 MHz, 0.3 W/cm2 HIFU at 48 h showed a quick and significant increase in PLX release (∼60%). Alike, PLA-PCN and PLX@PLA-PCN-224 exhibited high colloidal stability. Moreover, PLX@PLA-PCN-224 effectively penetrated the cells, resulting in significant ROS production upon HIFU exposure. PLX@PLA-PCN-224 (100 μg/ml) had considerably lower cell viability and higher apoptosis rate than PLX and PLA-PCN-224 at 24 h. Due to the upregulation of Bax/Bcl2 expression ratio on exposure of PLX@PLA-PCN-224 which increased the apoptotic cells rate. In vivo tumor bearing mice, H&E and TUNEL stained tissues of the PLX@PLA-PCN-224 groups with HIFU (+) therapy revealed tumor tissue damage and triggered tumor death compared to the control and HIFU (-) irradiation groups. This outcome highlights that PLX@PLA-PCN-224 as biologically compatible as well as effective cancer-targeted chemo-sonodynamic treatment.