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-SPION) 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-SPION nanoparticles 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.

Hyaluronic acid–nimesulide conjugates as anticancer drugs against CD44-overexpressing HT-29 colorectal cancer in vitro and in vivo

“…59,60 Besides, it was found that HA-NIR accumulated in the tumor region, indicating active targeting ability of HA in CD44 receptor overexpressing tumors. 61,62 HA-NIR was also found to be present in spleen and heart. To further investigate the differences in tumor accumulation between HAH-NIR and HAL-NIR at 48 h postinjection, the fluorescence intensity of isolated tumor ( Figure 6D) was analyzed by Living Image software.…”

Hyaluronan as a therapeutic target in human diseases

“…Furthermore, HA-based nanocarriers were investigated as drug vehicles for systemic targeting of CD44-overexpressed cancers [268, 269]. HA-coated superparamagnetic iron oxide nanoparticles conjugated anticancer drug doxorubicin was delivered at much higher levels and distributed wider in the tumor tissue than intravenously injected free doxorubicin, leading to significant reduction of tumor growth [270]. HA-Irinotecan was tested in a phase II trial to determine progression-free survival in 5-fluorouracil refractory patients with metastatic colorectal cancer [271].…”

Doxorubicin-Hyaluronan Conjugated Super-Paramagnetic Iron Oxide Nanoparticles (DOX-HA-SPION) Enhanced Cytoplasmic Uptake of Doxorubicin and Modulated Apoptosis, IL-6 Release and NF-kappaB Activity in Human MDA-MB-231 Breast Cancer Cells

“…44 DOX delivered by the HA-nanoparticle is much more potent than free DOX against ovarian cancer in vitro 44 and in vivo . 45–47 As CD44 is overexpressed in ER-/PR-/Her-2- or Triple Negative Breast Cancer (TNBC) cell lines. 48 We became interested in investigating whether HA coated nanoparticles can be utilized to enhance the drug efficacy against CD44-expressing TNBC cancer cells such as MDA-MB-231.…”