Assessing the in vivo efficacy of doxorubicin loaded hyaluronan nanoparticles.

Abstract

Magnetic nanoparticles are attractive platforms for biomedical applications including diagnosis and treatment of diseases. We have shown previously that hyaluronan-coated superparamagnetic iron oxide nanoparticles (HA-SPIONs) enhanced the efficacy of the conjugated anticancer drug doxorubicin (DOX) in vitro against drug-sensitive and drug-resistant human ovarian cancer cells. In this manuscript, we report our findings on the efficacy of DOX loaded HA-SPIONs in vivo using subcutaneous and intraperitoneal SKOV-3 ovarian tumor models in nude mice. The accumulation of the nanoparticles in subcutaneous tumors following an intravenous nanoparticle administration was confirmed by magnetic resonance imaging, and its distribution in the tumors was evaluated by confocal microscopy and Prussian blue staining. DOX delivered by nanoparticles accumulated at much higher levels and distributed wider in the tumor tissue than intravenously injected free DOX, leading to significant reduction of tumor growth. The IVIS Spectrum for in vivo bioluminescence imaging was used to aid in therapy assessment of the DOX-loaded nanoparticles on intraperitoneal ovarian tumors formed by firefly luciferase expressing human ovarian SKOV-3 cells. DOX-loaded HA-SPIONs significantly reduced tumor growth, delayed tumor development, and extended the survival of mice. Thus, utilizing HA-SPIONs as drug delivery vehicles constitutes a promising approach to tackle CD44 expressing ovarian cancer.