Oil/water nano-emulsion loaded with cobalt ferrite oxide nanocubes for photo-acoustic and magnetic resonance dual imaging in cancer: in vitro and preclinical studies

doi:10.1016/j.nano.2016.08.022

Nanomedicine: Nanotechnology, Biology and Medicine

Volume 13, Issue 1, January 2017, Pages 275-286

https://doi.org/10.1016/j.nano.2016.08.022 Get rights and content

Abstract

Dual imaging dramatically improves detection and early diagnosis of cancer. In this work we present an oil in water (O/W) nano-emulsion stabilized with lecithin and loaded with cobalt ferrite oxide (Co_0.5Fe_2.5O₄) nanocubes for photo-acoustic and magnetic resonance dual imaging. The nanocarrier is responsive in in vitro photo-acoustic and magnetic resonance imaging (MRI) tests. A clear and significant time-dependent accumulation in tumor tissue is shown in in vivo photo-acoustic studies on a murine melanoma xenograft model. The proposed O/W nano-emulsion exhibits also high values of r₂/r₁ (ranging from 45 to 85, depending on the magnetic field) suggesting a possible use as T₂ weighted image contrast agents. In addition, viability and cellular uptake studies show no significant cytotoxicity on the fibroblast cell line. We also tested the O/W nano-emulsion loaded with curcumin against melanoma cancer cells demonstrating a significant cytotoxicity and thus showing possible therapeutic effects in addition to the in vivo imaging.

Graphical Abstract

O/W nano-emulsions, embedding hydrophobic iron-cobalt oxide cubic nanoparticles (NPs), have been used, as photo-acoustic (PA) and MRI dual imaging diagnostic nanotool in cancer. Particularly, they show a PA response in vivo and a significant, time dependent, accumulation, post intravenous injection in tumor parenchyma of melanoma-bearing mice. In addition, shielding of encapsulated NPs decreases the r₁ improving the r₂/r₁ ratio in the range from 45 to 85 making possible a T₂ weighted imaging in MRI. Finally, curcumin loaded nano-emulsions provide significant cytotoxicity in melanoma cells showing possible therapy functionality of the proposed nanotool.

Section snippets

Materials

Soy-bean oil and Lipoid E80 lecithin were both purchased from Lipoid. Curcumin (from Curcuma longa [turmeric], powder, m.w. = 368.38), fluorescein 5(6)-isothiocyanate (FITC, m.w. = 389.38 g/mol), potassium ferrocyanide (II) trihydrate and Nuclear Fast Red were all purchased from Sigma Aldrich.

Synthesis

Co_0.5Fe_2.5O₄ nanocubes 20 nm in size were prepared following a thermal decomposition method recently published by our group.³⁴ The final decanoic acid capped nanocubes were dispersed in chloroform for further

Synthesis and physico-chemical characterization of the nanocarriers

To prepare the O/W nano-emulsion responsive to the photo-acoustic analysis, the oil core was loaded with Co_0.5Fe_2.5O₄ nanocubes. The nanometric size and the monodispersion of these nanoparticles was proved by TEM imaging, as reported in Figure 1 A and B. The difference in “brightness” of the nano-cubes is due to the fact that they are differently oriented with respect to the electron beam. Figure 1 A and B also shows cryo-TEM single projections of nanocubes embedded in oil nanodroplets of

Discussion

Thanks to its lipophilic properties, the proposed nanocarrier was able to embed hydrophobic surfactant coated iron-cobalt oxide nanocubes – as they were produced – without any further surface modification. Lecithin surfactant, which determined the emulsion size, was chosen on the basis of preliminary loading experiments showing that smaller nano-emulsion formulations induced precipitation of the iron-cobalt oxide NPs here used. The emulsion size obtained (~165 nm) is sufficiently large to

Acknowledgment

The authors thank Valentina La Tilla for the formatting of the figures, Roberta Infranca for the proofreading and Chiara Di Cicco for the preparation of one sample of nano-emulsion.

References (45)

A Hütten et al.
New magnetic nanoparticles for biotechnology
J Biotechnol
(2004)
AJ Cole et al.
Magnetic brain tumor targeting and biodistribution of long-circulating PEG-modified, cross-linked starch-coated iron oxide nanoparticles
Biomaterials
(2011)
S Ghosh et al.
The beneficial role of curcumin on inflammation, diabetes and neurodegenerative disease: a recent update
Food Chem Toxicol
(2015)
R Vecchione et al.
Curcumin bioavailability from oil in water nano-emulsions: in vitro and in vivo study on the dimensional, compositional and interactional dependence
J Control Release
(2016)
JR Kremer et al.
Computer visualization of three-dimensional image data using IMOD
J Struct Biol
(1996)
DN Mastronarde
Automated electron microscope tomography using robust prediction of specimen movements
J Struct Biol
(2005)
S Abbas et al.
Fabrication of polymeric nanocapsules from curcumin-loaded nanoemulsion templates by self-assembly
Ultrason Sonochem
(2015)
M Gaumet et al.
Nanoparticles for drug delivery: the need for precision in reporting particle size parameters
Eur J Pharm Biopharm
(2008)
E Papis et al.
Gene expression in nanotoxicology research: analysis by differential display in BALB3T3 fibroblasts exposed to cobalt particles and ions
Toxicol Lett
(2007)
B Chen et al.
Magnetic iron oxide nanoparticles for tumor-targeted therapy
Curr Cancer Drug Targets
(2011)

CSO Paulo et al.

Nanoparticles for intracellular-targeted drug delivery

Nanotechnology

(2011)

O Veiseh et al.

Optical and MRI multifunctional nanoprobe for targeting gliomas

Nano Lett

(2005)

BR Smith et al.

Localization to atherosclerotic plaque and biodistribution of biochemically derivatized superparamagnetic iron oxide nanoparticles (SPIONs) contrast particles for magnetic resonance imaging (MRI)

Biomed Microdevices

(2007)

H Qin et al.

Gadolinium(III)-gold nanorods for MRI and photoacoustic imaging dual-modality detection of macrophages in atherosclerotic inflammation

Nanomedicine

(2013)

A de la Zerda et al.

Photoacoustic ocular imaging

Opt Lett

(2010)

MP Melancon et al.

Theranostics with multifunctional magnetic gold nanoshells: photothermal therapy and t2* magnetic resonance imaging

Investig Radiol

(2011)

MF Kircher et al.

A brain tumor molecular imaging strategy using a new triple-modality MRI-photoacoustic-Raman nanoparticle

Nat Med

(2012)

FV Bunkin et al.

Optical excitation of sound waves

Sov Phys Acoust

(1973)

LV Wang et al.

Photoacoustic tomography: in vivo imaging from organelles to organs

Science

(2012)

X Wang et al.

Noninvasive laser-induced photoacoustic tomography for structural and functional in vivo imaging of the brain

Nat Biotechnol

(2003)

M Xu et al.

Photoacoustic imaging in biomedicine

Rev Sci Instrum

(2006)

D Wu et al.

Contrast agents for photoacoustic and thermoacoustic imaging: a review

Int J Mol Sci

(2014)

Cited by (36)

Stimuli-responsive switchable MRI nanoprobe for tumor theranostics
2023, Nano Today
With the advancement in magnetic resonance imaging (MRI) technology, traditional single T₁ or T₂ contrast agents struggle to meet the demend for accuracy imaging. In comparison, novel dual-mode contrast agents that possess T₁-T₂ ability, have the potential to provide excellent imaging applications, due to their capability of self-confirmation and cross-validation of MRI signal, ultimately resulting in improved accuracy of MRI imaging. Unlike traditional MRI contrast agents, which yield constant signal, causing excessive background noise, responsive MRI probes are designed to provide signals that change in response to stimuli. The use of stimuli-activated MRI probes combined with switchable T₁-T₂ MRI can lead to highly selective and excellent contrast effects for MRI contrast agents. This review focuses on the responsive and switchable MRI probe types, highlights the mechanism of MRI signal transformation, evaluates their application in tumor imaging or therapies, and provides a brief prediction of the future development tendencies and challenges associated with switchable MRI probes.
Photoacoustic spectroscopy and its applications to ferrite materials
2023, Ferrite Nanostructured Magnetic Materials: Technologies and Applications
Photoacoustic spectroscopy is a technique that enables one to detect light-induced heat production following the absorption of chopped radiation. This technique is nondestructive and provides unique possibilities for both applied and basic research ranging from fluorescence yield measurements, phase transitions, surface imaging, photo-induced mass transfer to the ultrasonic characterization of materials. In this chapter, its application to ferrite nanostructures is discussed.
Recent application of cobalt ferrite nanoparticles as a theranostic agent
2022, Materials Today Chemistry
Magnetic nanoparticles (MNPs) are highly appealing, particularly in the biomedical field. Nanoparticles made of iron oxide have gained a lot of attention in the last decade due to their elemental properties, which render them nontoxic and biodegradable. Other magnetic nanostructures, such as spinel ferrites, that may increase magnetic characteristics such as anisotropy and coercivity without sacrificing the intrinsic benefits of iron oxide nanoparticles have recently been investigated for broader MNP application. Cobalt ferrite (CoFe₂O₄) nanoparticles (NPs) are one of the most studied MNPs among the numerous spinel ferrites. Because CoFe₂O₄ nanostructures have theranostic properties, they are more effective than other nanostructured materials. Nanocarriers made of CoFe₂O₄ receive enhanced magnetic properties and are being tuned for their least toxic properties. As a result, the goal of this review is to give a thorough investigation of CoFe₂O₄ NPs and their specific uses, which make them ideal options for biosensing, imaging, fluorescent labeling, contrast effects, and hyperthermia.
A judicious review on the applications of chemotherapeutic loaded nanoemulsions in cancer management
2022, Journal of Drug Delivery Science and Technology
The escalating prevalence of cancer, a condition in which uncontrolled cell growth leads to complications and tissue failure, is one of the major concerns of healthcare professionals. The incompetence of the cytotoxic class of drugs to distinguish between the abnormally proliferating malignant cell mass and the quickly dividing healthy cells of the human body is one of their most catchy adverse effects. The increasing incidences of tumor cells resistant to conventional therapies such as chemotherapy and radiotherapy emphasize the critical need for anticancer drug delivery modalities. Among the devised nanocarriers, nanoemulsions are currently being envisaged as an effective drug delivery approach for an array of chemotherapeutics because of their unique attributes such as biodegradability, biocompatibility, nanometric size range with large surface area, optical clarity, non-immunogenicity, sustained-release behavior, ease of formulation and thermodynamic stability. As nanoemulsions are submicron emulsions with droplet sizes in the colloidal dispersion range, they have the added benefit of bypassing the anatomical and physiological constraints for drug delivery in the complex architecture of cancerous cells. Surface modification of nanoemulsions with targeting ligands, cell-penetrating components, stimuli-sensitive moieties, and fluorescent dye with a core capable of entrapping drugs, contrast agents, and imaging agents make it a smart nanocarrier and an apt choice among researchers from various domains to research upon. This review aims to furnish new insight on the application of nanoemulsions in cancer therapeutics. It also presents a list of challenges associated with the clinical translation of a nanoformulation.
Recent advances of emerging green chitosan-based biomaterials with potential biomedical applications: A review
2021, Carbohydrate Research
Citation Excerpt :
In this context, it is essential to reduce the use of hazardous compounds and increase the use of environmentally sustainable “green” materials in the production of nanoscale-based composite materials by using clear and green chemical synthesis routes [1]. Furthermore, nanotechnology's advent provides inventive and excellent opportunities for the treatment of various pharmaceutical applications such as in vaccination, tissue engineering, diagnostic imaging procedures, cancer therapy, and other medicinal, and sustainable drug delivery, etc [2–4]. Liposomes, nanocapsules, nanoparticles, polymeric micelles, nano-structured lipid carriers, inorganic nanoparticles, and solid lipid nanoparticles have been the most scientifically relevant nanomaterials at the time [5,6].
Chitosan is the most abundant natural biopolymer, after cellulose. It is mainly derived from the fungi, shrimp's shells, and exoskeleton of crustaceans, through the deacetylation of chitin. The ecological sustainability associated with its exercise and the flexibility of chitosan owing to its active functional hydroxyl and amino groups makes it a promising candidate for a wide range of applications through a variety of modifications. The biodegradability and biocompatibility of chitosan and its derivatives along with their various chemical functionalities make them promising carriers for pharmaceutical, nutritional, medicinal, environmental, agriculture, drug delivery, and biotechnology applications. The present work aims to provide a detailed and organized description of modified chitosan and its derivatives-based nanomaterials for biomedical applications. We addressed the biological and physicochemical benefits of nanocomposite materials made up of chitosan and its derivatives in various formulations, including improved physicochemical stability and cells/tissue interaction, controlled drug release, and increased bioavailability and efficacy in clinical practice. Moreover, several modification techniques and their effective utilization are also reviewed and collected in this review.
Theranostic application of nanoemulsions in chemotherapy
2020, Drug Discovery Today
Citation Excerpt :
Recently, Vecchione et al. reported preclinical experiments using cobalt ferrite oxide within the core of a nanoemulsion for dual imaging of cancer (MRI and photoacoustic) in xenografted murine melanoma models. The authors incorporated curcumin, a herbal flavonoid from the rhizome of Curcuma longa, within the oil nanoemulsion, and reported significant cytotoxicity against melanoma cell lines, suggesting a possible combination of therapeutic and diagnostic applications [89]. Overall, a smaller particle size with the option to modify the architecture based on need provides flexibility to nanoemulsion dosage forms, making them attractive for theranostic applications in cancer.
Theranostics has the potential to revolutionize the diagnosis, treatment, and prognosis of cancer, where novel drug delivery systems could be used to detect the disease at an early stage with instantaneous treatment. Various preclinical approaches of nanoemulsions with entrapped contrast and chemotherapeutic agents have been documented to act specifically on the tumor microenvironment (TME) for both diagnostic and therapeutic purposes. However, bringing these theranostic nanoemulsions through preclinical trials to patients requires several fundamental hurdles to be overcome, including the in vivo behavior of the delivery tool, degradation, and clearance from the system, as well as long-term toxicities. Here, we discuss recent advances in the application of nanoemulsions in molecular imaging with simultaneous therapeutic efficacy in a single delivery system.

View all citing articles on Scopus

: The authors are grateful for financial support from the Italian AIRC project (contract no. 14527 to T.P.) and EU-ITN network Mag(NET)icFun (PITN-GA-2012-290248).

¹: Raffaele Vecchione and Vincenzo Quagliariello contributed equally to this work.

View full text

Original ArticleOil/water nano-emulsion loaded with cobalt ferrite oxide nanocubes for photo-acoustic and magnetic resonance dual imaging in cancer: in vitro and preclinical studies