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

Abstract

Triple negative breast cancer exhibit increased IL-6 expression compared with matched healthy breast tissue and a strong link between inflammation and cancer progression and metastasis has been reported. We investigated whether doxorubicin-hyaluronan-super-paramagnetic iron oxide nanoparticles (DOX-HA-SPION) would show greater therapeutic efficacy in human triple negative breast cancer cells (TNBC) MDA-MB-231, as was recently shown in drug-sensitive and multidrug-resistant ovarian cancer cells. Therefore, we measured cellular DOX uptake via confocal microscopy; observed morphologic changes: mitochondrial and nuclear changes with electron microscopy, and quantitated apoptosis using FACS analysis after Annexin V and PI staining in MDA-MB-231 cells treated with either DOX alone or DOX-HA-SPION. We also measured both proinflammatory and anti-inflammatory cytokines; IL-6, IL-10 respectively and also measured nitrate levels in the conditioned medium by ELISA. Inaddition, NF-kB activity was measured by luciferase assay. Confocal microscopy demonstrated greater cytoplasmic uptake of DOX-HA-SPION than free DOX. We also demonstrated reduction of Vimentin with DOX-HA-SPION which is significantly less than both control and DOX. DOX-HA-SPION enhanced apoptosis and significantly down regulated both pro-inflammatory mediators IL-6 and NF-kB in comparison to DOX alone. The secretion levels of anti-inflammatory mediators IL-10 and nitrate was not decreased in the DOX or DOX-HA-SPION treatment groups. Our data suggest that DOX-HA-SPION nanomedicine-based drug delivery could have promising potential in treating metastasized and chemoresistant breast cancer by enhancing the drug efficacy and minimizing off-target effects.

Doxorubicin-Bioconjugated Cadmium Sulfide Dextrin Quantum Dots for Imaging Cells

“…7A). Previous studies using DOX-conjugated nanoparticles have shown that the cytotoxic effect of DOX is preserved and capable of inducing both apoptosis and necrosis in different cell lines [43][44][45][46] . On the other hand, other studies have explained that QDs-based distribution of DOX enabled cell expansion and as a consequence, yielded better pharmacological results [44] .…”

Rapid Extensive Recurrence of Triple Negative Breast Cancer: Are Both Therapy and Cancer Biology the Culprit?

“…Several studies also demonstrate that chemotherapy drug effects on adipose tissue may be mediated by DOX-induced activation of NFκB and inflammatory cytokines [ 18 , 19 ]. Studies on rodent models demonstrated that DOX increases serum total cholesterol, triglyceride and LDL levels when compared to controls [ 20-22 ].…”

Triple-Negative Breast Cancer: A Review of Conventional and Advanced Therapeutic Strategies

“…SPIONs have higher magnetic properties than paramagnetic materials due to their ability to spin alignment to an external magnetic field SPIONs can generate heat inside the tumors producing apoptosis by using hyperthermia as well as real time images into the tumors [195] Experimental/clinicalongoing SPIONs are often use in human triple-negative breast cancer cells (TNBC) MDA-MB-231 therapeutics [209]. Table 2.…”