Tailored Functionalized Magnetic Nanoparticles to Target Breast Cancer Cells Including Cancer Stem-Like Cells

Abstract

Nanotechnology-based approaches hold substantial potential to avoid chemoresistance and minimize side effects. In this work, we have used biocompatible iron oxide magnetic nanoparticles (MNPs) called MF66 and functionalized with the antineoplastic drug doxorubicin (DOX) against MDA-MB-231 cells. Electrostatically functionalized MNPs showed effective uptake and DOX linked to MNPs was more efficiently retained inside the cells than free DOX, leading to cell inactivation by mitotic catastrophe, senescence and apoptosis. Both effects, uptake and cytotoxicity, were demonstrated by different assays and videomicroscopy techniques. Likewise, covalently functionalized MNPs using three different linkers—disulfide (DOX-S-S-Pyr, called MF66-S-S-DOX), imine (DOX-I-Mal, called MF66-I-DOX) or both (DOX-I-S-S-Pyr, called MF66-S-S-I-DOX)—were also analysed. The highest cell death was detected using a linker sensitive to both pH and reducing environment (DOX-I-S-S-Pyr). The greatest success of this study was to detect also their activity against breast cancer stem-like cells (CSC) from MDA-MB-231 and primary breast cancer cells derived from a patient with a similar genetic profile (triple-negative breast cancer). In summary, these nanoformulations are promising tools as therapeutic agent vehicles, due to their ability to produce efficient internalization, drug delivery, and cancer cell inactivation, even in cancer stem-like cells (CSCs) from patients.

Smart Modification on Magnetic Nanoparticles Dramatically Enhances Their Therapeutic Properties

“…Hence, our proposed nanocarrier offers a potential solution to avoid the toxicity and the lack of effectiveness of gemcitabine in its clinical use [3,4] and it is expected to remain intact in blood circulation [50]. The stability and efficacy of disulfidebased drug delivery systems have been widely studied, showing promising results in breast cancer [51], uveal melanoma [52], and pancreatic cancer models [19], among others.…”

Quantum Dots as a Good Carriers of Unsymmetrical Bisacridines for Modulating Cellular Uptake and the Biological Response in Lung and Colon Cancer Cells

“…To the best of our knowledge, no previous reports have investigated the influence of anticancer drugs conjugated with QDs on the induction of cellular senescence. Further, only a few studies have shown the influence of drugs (e.g., doxorubicin; DOX) conjugated with other NPs on the induction of senescence [ 37 ]. Lazaro-Carrillo A. et al showed that iron oxide magnetic NPs (MF66) alone did not induce senescence in MDA-MB-231 cancer cells.…”

Dual-Functionalized Nanoliposomes Achieve a Synergistic Chemo-Phototherapeutic Effect

“…The cell cycle of photodynamic treated cells grown in F25 flasks was evaluated at different post-irradiation times (12, 24, and 72 h), as previously described [ 77 ].…”