Antitumor Effects of Intra-Arterial Delivery of Albumin-Doxorubicin Nanoparticle Conjugated Microbubbles Combined with Ultrasound-Targeted Microbubble Activation on VX2 Rabbit Liver Tumors

Abstract

Image-guided intra-arterial therapies play a key role in the management of hepatic malignancies. However, limited clinical outcomes suggest the need for new multifunctional drug delivery systems to enhance local drug concentration while reducing systemic adverse reactions. Therefore, we developed the albumin-doxorubicin nanoparticle conjugated microbubble (ADMB) to enhance therapeutic efficiency by sonoporation under exposure to ultrasound. ADMB demonstrated a size distribution of 2.33 ± 1.34 µm and a doxorubicin loading efficiency of 82.7%. The echogenicity of ADMBs was sufficiently generated in the 2–9 MHz frequency range and cavitation depended on the strength of the irradiating ultrasound. In the VX2 rabbit tumor model, ADMB enhanced the therapeutic efficiency under ultrasound exposure, compared to free doxorubicin. The intra-arterial administration of ADMBs sufficiently reduced tumor growth by five times, compared to the control group. Changes in the ADC values and viable tumor fraction supported the fact that the antitumor effect of ADMBs were enhanced by evidence of necrosis ratio (over 70%) and survival tumor cell fraction (20%). Liver toxicity was comparable to that of conventional therapies. In conclusion, this study shows that tumor suppression can be sufficiently maximized by combining ultrasound exposure with intra-arterial ADMB administration.

UTMD inhibit EMT of breast cancer through the ROS/miR-200c/ZEB1 axis

“…Various studies have proved that UTMD suppresses the progression of carcinoma, and sonoporation-induced biological barrier permeability has emerged as a pivotal mechanism of UTMD in tumor progression repression 9,14,25 . To explore whether there is any other mechanism of UTMD-inhibited tumor progression, we investigated the role of UTMD in inhibiting breast cancer EMT and tried to reveal its mechanism.…”

<p>Ultrasound Assisted a Peroxisome Proliferator-Activated Receptor (PPAR)γ Agonist-Loaded Nanoparticle-Microbubble Complex to Attenuate Renal Interstitial Fibrosis</p>

“…15 In recent years, the use of nanoparticles as coating materials for MBs has attracted increasing attention in many studies. [16][17][18] To the best of our knowledge, there is no study to date combining US exposure with MB-coupled drug-loaded nanoparticles for the treatment of renal diseases. Polylactide-co-glycolide (PLGA) is a common biodegradable material that has been approved by the US Food and Drug Administration for widely used in clinical applications; PLGA nanoparticles (PLNPs) have been extensively studied as drug delivery vehicles and also been used to treat renal fibrosis.…”

Anti-Tumor Drug-Loaded Oxygen Nanobubbles for the Degradation of HIF-1α and the Upregulation of Reactive Oxygen Species in Tumor Cells

“…Microbubbles and nanobubbles are composed of a stabilizing monolayered shell and a gas core, and have a long history of use as contrast agents in ultrasound [24,25,26,27,28,29,30,31,32]. Over the past two decades, more attention has been paid to the use of microbubbles for therapeutic purposes because of their biocompatibility, smaller size, ability to deliver drugs and gases, higher surface contact area, and variety of compositions [33,34,35,36,37,38,39]. Various researchers have used microbubbles and nanobubbles to deliver oxygen gas to overcome hypoxia and hypoxemia [28,40,41,42,43,44,45,46].…”