In Vivo Assimilation of CuS, Iron Oxide and Iron Oxide@CuS Nanoparticles in Mice: A 6-Month Follow-Up Study.

Alberto Curcio,Aurore Van De Walle,Ali Abou-Hassan,Claire Wilhelm,Christine Péchoux

doi:10.3390/pharmaceutics14010179

Abstract

Nanoparticles (NPs) are at the leading edge of nanomedicine, and determining their biosafety remains a mandatory precondition for biomedical applications. Herein, we explore the bioassimilation of copper sulfide NPs reported as powerful photo-responsive anticancer therapeutic agents. The nanoparticles investigated present a hollow shell morphology, that can be left empty (CuS NPs) or be filled with an iron oxide flower-like core (iron oxide@CuS NPs), and are compared with the iron oxide nanoparticles only (iron oxide NPs). CuS, iron oxide@CuS and iron oxide NPs were injected in 6-week-old mice, at doses coherent with an antitumoral treatment. Cu and Fe were quantified in the liver, spleen, kidneys, and lungs over 6 months, including the control animals, thus providing endogenous Cu and Fe levels in the first months after animal birth. After intravenous NPs administration, 77.0 ± 3.9% of the mass of Cu injected, and 78.6 ± 3.8% of the mass of Fe, were detected in the liver. In the spleen, we found 3.3 ± 0.6% of the injected Cu and 3.8 ± 0.6% for the Fe. No negative impact was observed on organ weight, nor on Cu or Fe homeostasis in the long term. The mass of the two metals returned to the control values within three months, a result that was confirmed by transmission electron microscopy and histology images. This bioassimilation with no negative impact comforts the possible translation of these nanomaterials into clinical practice.

Highlights

Metal sulfide nanoparticles (NPs) possess versatile optical and electronic properties, making them attractive for varied applications that include energy conversion and storage in solar cells [1,2,3], catalysts for industrial transformations, or carriers for drug delivery [4].the toxicity of semiconductor NPs (e.g., ZnS and CdS) has been a limit to the range of possible applications, in particular in the biomedical area
In addition to their low toxicity [5], those nanostructures can be stimulated using near-infrared (NIR) light, an advantage in the biomedical field as it allows deep penetration into biological tissues, with minimal photodamage to the cells [4]. Their absorption in both the 650–950 nm range (NIR I region) and in the second NIR region (1000–1700 nm, NIR II), where light absorption by tissues and photon scattering is lower, is valuable. This property is explored for photoacoustic imaging [6,7,8], as photothermal switch to activate signaling pathways [9], and for the photothermal ablation of cancer cells [10,11]
Quantification of endogenous iron and copper mass was performed on the control mice

Summary

Introduction

Metal sulfide nanoparticles (NPs) possess versatile optical and electronic properties, making them attractive for varied applications that include energy conversion and storage in solar cells [1,2,3], catalysts for industrial transformations, or carriers for drug delivery [4].the toxicity of semiconductor NPs (e.g., ZnS and CdS) has been a limit to the range of possible applications, in particular in the biomedical area. Copper sulfide (CuS) NPs have received increased interest in recent years In addition to their low toxicity [5], those nanostructures can be stimulated using near-infrared (NIR) light, an advantage in the biomedical field as it allows deep penetration into biological tissues, with minimal photodamage to the cells [4]. Their absorption in both the 650–950 nm range (NIR I region) and in the second NIR region (1000–1700 nm, NIR II), where light absorption by tissues and photon scattering is lower, is valuable. This property is explored for photoacoustic imaging [6,7,8], as photothermal switch to activate signaling pathways [9], and for the photothermal ablation of cancer cells [10,11]

Methods

Results

Conclusion