Tailored-Made Polydopamine Nanoparticles to Induce Ferroptosis in Breast Cancer Cells in Combination with Chemotherapy.

Celia Nieto,Eva M Martín Del Valle,Milena A Vega

doi:10.3390/ijms22063161

Celia Nieto, Eva M Martín Del Valle + Show 1 more

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https://doi.org/10.3390/ijms22063161

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Abstract

Ferroptosis is gaining followers as mechanism of selective killing cancer cells in a non-apoptotic manner, and novel nanosystems capable of inducing this iron-dependent death are being increasingly developed. Among them, polydopamine nanoparticles (PDA NPs) are arousing interest, since they have great capability of chelating iron. In this work, PDA NPs were loaded with Fe3+ at different pH values to assess the importance that the pH may have in determining their therapeutic activity and selectivity. In addition, doxorubicin was also loaded to the nanoparticles to achieve a synergist effect. The in vitro assays that were performed with the BT474 and HS5 cell lines showed that, when Fe3+ was adsorbed in PDA NPs at pH values close to which Fe(OH)3 begins to be formed, these nanoparticles had greater antitumor activity and selectivity despite having chelated a smaller amount of Fe3+. Otherwise, it was demonstrated that Fe3+ could be released in the late endo/lysosomes thanks to their acidic pH and their Ca2+ content, and that when Fe3+ was co-transported with doxorubicin, the therapeutic activity of PDA NPs was enhanced. Thus, reported PDA NPs loaded with both Fe3+ and doxorubicin may constitute a good approach to target breast tumors.

Highlights

In recent decades, extensive efforts have been made by the scientific community to find novel, more efficient, effective, and tolerable cancer therapies [1]
PDA NPs were prepared using the standard procedure of oxidative polymerization of dopamine in a basic aqueous medium containing ethanol (27.7% V/V) and NH4OH (2.9% V/V) [13,17,18]
PDA NPs were characterized by TEM and a size-range histogram was obtained, from which it was determined that NPs had an average size of 111.2 ± 16.2 nm (Figure 1a)

Summary

Introduction

Extensive efforts have been made by the scientific community to find novel, more efficient, effective, and tolerable cancer therapies [1]. Most developed nanotherapies are only focused on inducing programmed death of cancer cells and these are able to combat the apoptosis pathway many times, so that multidrug resistance (MDR) occurs more frequently than desired [3]. For this reason, recent studies have suggested that targeting biochemical alterations in cancer cells, in combination or not with the employment of pro-apoptotic agents, may be a feasible and efficacious approach to selectively treat cancer and prevent the apparition of MDR [2,4]. The import, storage and export pathways of Fe, which are tightly regulated in healthy cells (with no excretory route for excess Fe), are perturbed in tumors to maintain increased Fe levels in these tissues [7]

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