Research

18 pages, 33494 KiB

Open AccessArticle

In Vitro Studies of Pegylated Magnetite Nanoparticles in a Cellular Model of Viral Oncogenesis: Initial Studies to Evaluate Their Potential as a Future Theranostic Tool

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María G. Montiel Schneider

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Verónica Lassalle

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Verónica González-Pardo

Pharmaceutics 2023, 15(2), 488; https://doi.org/10.3390/pharmaceutics15020488 - 01 Feb 2023

Viewed by 970

Abstract

Magnetic nanosystems represent promising alternatives to the traditional diagnostic and treatment procedures available for different pathologies. In this work, a series of biological tests are proposed, aiming to validate a magnetic nanoplatform for Kaposi’s sarcoma treatment. The selected nanosystems were polyethylene glycol-coated iron [...] Read more.

Magnetic nanosystems represent promising alternatives to the traditional diagnostic and treatment procedures available for different pathologies. In this work, a series of biological tests are proposed, aiming to validate a magnetic nanoplatform for Kaposi’s sarcoma treatment. The selected nanosystems were polyethylene glycol-coated iron oxide nanoparticles (MAG.PEG), which were prepared by the hydrothermal method. Physicochemical characterization was performed to verify their suitable physicochemical properties to be administered in vivo. Exhaustive biological assays were conducted, aiming to validate this platform in a specific biomedical field related to viral oncogenesis diseases. As a first step, the MAG.PEG cytotoxicity was evaluated in a cellular model of Kaposi’s sarcoma. By phase contrast microscopy, it was found that cell morphology remained unchanged regardless of the nanoparticles’ concentration (1–150 µg mL⁻¹). The results, arising from the crystal violet technique, revealed that the proliferation was also unaffected. In addition, cell viability analysis by MTS and neutral red assays revealed a significant increase in metabolic and lysosomal activity at high concentrations of MAG.PEG (100–150 µg mL⁻¹). Moreover, an increase in ROS levels was observed at the highest concentration of MAG.PEG. Second, the iron quantification assays performed by Prussian blue staining showed that MAG.PEG cellular accumulation is dose dependent. Furthermore, the presence of vesicles containing MAG.PEG inside the cells was confirmed by TEM. Finally, the MAG.PEG steering was achieved using a static magnetic field generated by a moderate power magnet. In conclusion, MAG.PEG at a moderate concentration would be a suitable drug carrier for Kaposi’s sarcoma treatment, avoiding adverse effects on normal tissues. The data included in this contribution appear as the first stage in proposing this platform as a suitable future theranostic to improve Kaposi’s sarcoma therapy. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials – a Promising Approach in Cancer Therapy)

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23 pages, 8932 KiB

Open AccessArticle

Study of Cytotoxicity and Internalization of Redox-Responsive Iron Oxide Nanoparticles on PC-3 and 4T1 Cancer Cell Lines

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Elizaveta S. Permyakova

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Pavel S. Mogilnikov

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Daniil A. Vishnevskiy

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Igor V. Shchetinin

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Maxim A. Abakumov

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Alexander G. Savchenko

Pharmaceutics 2023, 15(1), 127; https://doi.org/10.3390/pharmaceutics15010127 - 30 Dec 2022

Viewed by 1901

Abstract

Redox-responsive and magnetic nanomaterials are widely used in tumor treatment separately, and while the application of their combined functionalities is perspective, exactly how such synergistic effects can be implemented is still unclear. This report investigates the internalization dynamics of magnetic redox-responsive nanoparticles (MNP-SS) [...] Read more.

Redox-responsive and magnetic nanomaterials are widely used in tumor treatment separately, and while the application of their combined functionalities is perspective, exactly how such synergistic effects can be implemented is still unclear. This report investigates the internalization dynamics of magnetic redox-responsive nanoparticles (MNP-SS) and their cytotoxicity toward PC-3 and 4T1 cell lines. It is shown that MNP-SS synthesized by covalent grafting of polyethylene glycol (PEG) on the magnetic nanoparticle (MNP) surface via SS-bonds lose their colloidal stability and aggregate fully in a solution containing DTT, and partially in conditioned media, whereas the PEGylated MNP (MNP-PEG) without S-S linker control remains stable under the same conditions. Internalized MNP-SS lose the PEG shell more quickly, causing enhanced magnetic core dissolution and thus increased toxicity. This was confirmed by fluorescence microscopy using MNP-SS dual-labeled by Cy3 via labile disulfide, and Cy5 via a rigid linker. The dyes demonstrated a significant difference in fluorescence dynamics and intensity. Additionally, MNP-SS demonstrate quicker cellular uptake compared to MNP-PEG, as confirmed by TEM analysis. The combination of disulfide bonds, leading to faster dissolution of the iron oxide core, and the high-oxidative potential Fe³⁺ ions can synergically enhance oxidative stress in comparison with more stable coating without SS-bonds in the case of MNP-PEG. It decreases the cancer cell viability, especially for the 4T1, which is known for being sensitive to ferroptosis-triggering factors. In this work, we have shown the effect of redox-responsive grafting of the MNP surface as a key factor affecting MNP-internalization rate and dissolution with the release of iron ions inside cancer cells. This kind of synergistic effect is described for the first time and can be used not only in combination with drug delivery, but also in treatment of tumors responsive to ferroptosis. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials – a Promising Approach in Cancer Therapy)

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24 pages, 4384 KiB

Open AccessArticle

Biologic Impact of Green Synthetized Magnetic Iron Oxide Nanoparticles on Two Different Lung Tumorigenic Monolayers and a 3D Normal Bronchial Model—EpiAirway^TM Microtissue

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Elena-Alina Moacă

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Claudia Watz

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Alexandra-Corina Faur

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Cristina Adriana Dehelean

Pharmaceutics 2023, 15(1), 2; https://doi.org/10.3390/pharmaceutics15010002 - 20 Dec 2022

Cited by 1 | Viewed by 1102

Abstract

The present study reports the successful synthesis of biocompatible magnetic iron oxide nanoparticles (MNPs) by an ecofriendly single step method, using two ethanolic extracts based on leaves of Camellia sinensis L. and Ocimum basilicum L. The effect of both green raw materials as [...] Read more.

The present study reports the successful synthesis of biocompatible magnetic iron oxide nanoparticles (MNPs) by an ecofriendly single step method, using two ethanolic extracts based on leaves of Camellia sinensis L. and Ocimum basilicum L. The effect of both green raw materials as reducing and capping agents was taken into account for the development of MNPs, as well as the reaction synthesis temperature (25 °C and 80 °C). The biological effect of the MNPs obtained from Camellia sinensis L. ethanolic extract (Cs 25, Cs 80) was compared with that of the MNPs obtained from Ocimum basilicum L. ethanolic extract (Ob 25, Ob 80), by using two morphologically different lung cancer cell lines (A549 and NCI-H460); the results showed that the higher cell viability impairment was manifested by A549 cells after exposure to MNPs obtained from Ocimum basilicum L. ethanolic extract (Ob 25, Ob 80). Regarding the biosafety profile of the MNPs, it was shown that the EpiAirway^TM models did not elicit important viability decrease or significant histopathological changes after treatment with none of the MNPs (Cs 25, Cs 80 and Ob 25, Ob 80), at concentrations up to 500 µg/mL. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials – a Promising Approach in Cancer Therapy)

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22 pages, 9265 KiB

Open AccessArticle

Effect of the Silica–Magnetite Nanocomposite Coating Functionalization on the Doxorubicin Sorption/Desorption

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Alexander M. Demin

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Alexander V. Vakhrushev

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Konstantin A. Chistyakov

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Galina L. Levit

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Victor P. Krasnov

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Valery N. Charushin

Pharmaceutics 2022, 14(11), 2271; https://doi.org/10.3390/pharmaceutics14112271 - 24 Oct 2022

Cited by 5 | Viewed by 1288

Abstract

A series of new composite materials based on Fe₃O₄ magnetic nanoparticles coated with SiO₂ (or aminated SiO₂) were synthesized. It has been shown that the use of N-(phosphonomethyl)iminodiacetic acid (PMIDA) to stabilize nanoparticles before silanization ensures [...] Read more.

A series of new composite materials based on Fe₃O₄ magnetic nanoparticles coated with SiO₂ (or aminated SiO₂) were synthesized. It has been shown that the use of N-(phosphonomethyl)iminodiacetic acid (PMIDA) to stabilize nanoparticles before silanization ensures the increased content of a SiO₂ phase in the Fe₃O₄@SiO₂ nanocomposites (NCs) in comparison with materials obtained under similar conditions, but without PMIDA. It has been demonstrated for the first time that the presence of PMIDA on the surface of NCs increases the level of Dox loading due to specific binding, while surface modification with 3-aminopropylsilane, on the contrary, significantly reduces the sorption capacity of materials. These regularities were in accordance with the results of quantum chemical calculations. It has been shown that the energies of Dox binding to the functional groups of NCs are in good agreement with the experimental data on the Dox sorption on these NCs. The mechanisms of Dox binding to the surface of NCs were proposed: simultaneous coordination of Dox on the PMIDA molecule and silanol groups at the NC surface leads to a synergistic effect in Dox binding. The synthesized NCs exhibited pH-dependent Dox release, as well as dose-dependent cytotoxicity in in vitro experiments. The cytotoxic effects of the studied materials correspond to their calculated IC₅₀ values. NCs with a SiO₂ shell obtained using PMIDA exhibited the highest effect. At the same time, the presence of PMIDA in NCs makes it possible to increase the Dox loading, as well as to reduce its desorption rate, which may be useful in the design of drug delivery vehicles with a prolonged action. We believe that the data obtained can be further used to develop stimuli-responsive materials for targeted cancer chemotherapy. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials – a Promising Approach in Cancer Therapy)

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25 pages, 11795 KiB

Open AccessArticle

The Effect of Zn-Substitution on the Morphological, Magnetic, Cytotoxic, and In Vitro Hyperthermia Properties of Polyhedral Ferrite Magnetic Nanoparticles

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Constantin Mihai Lucaciu

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Felicia Loghin

Pharmaceutics 2021, 13(12), 2148; https://doi.org/10.3390/pharmaceutics13122148 - 14 Dec 2021

Cited by 9 | Viewed by 2144

Abstract

The clinical translation of magnetic hyperthermia (MH) needs magnetic nanoparticles (MNPs) with enhanced heating properties and good biocompatibility. Many studies were devoted lately to the increase in the heating power of iron oxide MNPs by doping the magnetite structure with divalent cations. A [...] Read more.

The clinical translation of magnetic hyperthermia (MH) needs magnetic nanoparticles (MNPs) with enhanced heating properties and good biocompatibility. Many studies were devoted lately to the increase in the heating power of iron oxide MNPs by doping the magnetite structure with divalent cations. A series of MNPs with variable Zn/Fe molar ratios (between 1/10 and 1/1) were synthesized by using a high-temperature polyol method, and their physical properties were studied with different techniques (Transmission Electron Microscopy, X-ray diffraction, Fourier Transform Infrared Spectroscopy). At low Zn doping (Zn/Fe ratio 1/10), a significant increase in the saturation magnetization (90 e.m.u./g as compared to 83 e.m.u./g for their undoped counterparts) was obtained. The MNPs’ hyperthermia properties were assessed in alternating magnetic fields up to 65 kA/m at a frequency of 355 kHz, revealing specific absorption rates of up to 820 W/g. The Zn ferrite MNPs showed good biocompatibility against two cell lines (A549 cancer cell line and BJ normal cell line) with a drop of only 40% in the viability at the highest dose used (500 μg/cm²). Cellular uptake experiments revealed that the MNPs enter the cells in a dose-dependent manner with an almost 50% higher capacity of cancer cells to accommodate the MNPs. In vitro hyperthermia data performed on both cell lines indicate that the cancer cells are more sensitive to MH treatment with a 90% drop in viability after 30 min of MH treatment at 30 kA/m for a dose of 250 μg/cm². Overall, our data indicate that Zn doping of iron oxide MNPs could be a reliable method to increase their hyperthermia efficiency in cancer cells. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials – a Promising Approach in Cancer Therapy)

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19 pages, 3618 KiB

Open AccessArticle

Drug Release Profiles of Mitomycin C Encapsulated Quantum Dots–Chitosan Nanocarrier System for the Possible Treatment of Non-Muscle Invasive Bladder Cancer

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Fariza Aina Abd Manan

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Pharmaceutics 2021, 13(9), 1379; https://doi.org/10.3390/pharmaceutics13091379 - 31 Aug 2021

Cited by 18 | Viewed by 2912

Abstract

Nanotechnology-based drug delivery systems are an emerging technology for the targeted delivery of chemotherapeutic agents in cancer therapy with low/no toxicity to the non-cancer cells. With that view, the present work reports the synthesis, characterization, and testing of Mn:ZnS quantum dots (QDs) conjugated [...] Read more.

Nanotechnology-based drug delivery systems are an emerging technology for the targeted delivery of chemotherapeutic agents in cancer therapy with low/no toxicity to the non-cancer cells. With that view, the present work reports the synthesis, characterization, and testing of Mn:ZnS quantum dots (QDs) conjugated chitosan (CS)-based nanocarrier system encapsulated with Mitomycin C (MMC) drug. This fabricated nanocarrier, MMC@CS-Mn:ZnS, has been tested thoroughly for the drug loading capacity, drug encapsulation efficiency, and release properties at a fixed wavelength (358 nm) using a UV–Vis spectrophotometer. Followed by the physicochemical characterization, the cumulative drug release profiling data of MMC@CS-Mn:ZnS nanocarrier (at pH of 6.5, 6.8, 7.2, and 7.5) were investigated to have the highest release of 56.48% at pH 6.8, followed by 50.22%, 30.88%, and 10.75% at pH 7.2, 6.5, and 7.5, respectively. Additionally, the drug release studies were fitted to five different pharmacokinetic models including pesudo-first-order, pseudo-second-order, Higuchi, Hixson–Crowell, and Korsmeyers–Peppas models. From the analysis, the cumulative MMC release suits the Higuchi model well, revealing the diffusion-controlled mechanism involving the correlation of cumulative drug release proportional to the function square root of time at equilibrium, with the correlation coefficient values (R²) of 0.9849, 0.9604, 0.9783, and 0.7989 for drug release at pH 6.5, 6.8, 7.2, and 7.5, respectively. Based on the overall results analysis, the formulated nanocarrier system of MMC synergistically envisages the efficient delivery of chemotherapeutic agents to the target cancerous sites, able to sustain it for a longer time, etc. Consequently, the developed nanocarrier system has the capacity to improve the drug loading efficacy in combating the reoccurrence and progression of cancer in non-muscle invasive bladder diseases. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials – a Promising Approach in Cancer Therapy)

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Review

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49 pages, 6049 KiB

Open AccessReview

A Review of Advanced Multifunctional Magnetic Nanostructures for Cancer Diagnosis and Therapy Integrated into an Artificial Intelligence Approach

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Bharath Govindan

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Muhammad Ashraf Sabri

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Abdul Hai

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Fawzi Banat

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Mohammad Abu Haija

Pharmaceutics 2023, 15(3), 868; https://doi.org/10.3390/pharmaceutics15030868 - 07 Mar 2023

Cited by 12 | Viewed by 3122

Abstract

The new era of nanomedicine offers significant opportunities for cancer diagnostics and treatment. Magnetic nanoplatforms could be highly effective tools for cancer diagnosis and treatment in the future. Due to their tunable morphologies and superior properties, multifunctional magnetic nanomaterials and their hybrid nanostructures [...] Read more.

The new era of nanomedicine offers significant opportunities for cancer diagnostics and treatment. Magnetic nanoplatforms could be highly effective tools for cancer diagnosis and treatment in the future. Due to their tunable morphologies and superior properties, multifunctional magnetic nanomaterials and their hybrid nanostructures can be designed as specific carriers of drugs, imaging agents, and magnetic theranostics. Multifunctional magnetic nanostructures are promising theranostic agents due to their ability to diagnose and combine therapies. This review provides a comprehensive overview of the development of advanced multifunctional magnetic nanostructures combining magnetic and optical properties, providing photoresponsive magnetic platforms for promising medical applications. Moreover, this review discusses various innovative developments using multifunctional magnetic nanostructures, including drug delivery, cancer treatment, tumor-specific ligands that deliver chemotherapeutics or hormonal agents, magnetic resonance imaging, and tissue engineering. Additionally, artificial intelligence (AI) can be used to optimize material properties in cancer diagnosis and treatment, based on predicted interactions with drugs, cell membranes, vasculature, biological fluid, and the immune system to enhance the effectiveness of therapeutic agents. Furthermore, this review provides an overview of AI approaches used to assess the practical utility of multifunctional magnetic nanostructures for cancer diagnosis and treatment. Finally, the review presents the current knowledge and perspectives on hybrid magnetic systems as cancer treatment tools with AI models. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials – a Promising Approach in Cancer Therapy)

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32 pages, 5946 KiB

Open AccessEditor’s ChoiceReview

Superparamagnetic Iron Oxide Nanoparticles (SPION): From Fundamentals to State-of-the-Art Innovative Applications for Cancer Therapy

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Pharmaceutics 2023, 15(1), 236; https://doi.org/10.3390/pharmaceutics15010236 - 10 Jan 2023

Cited by 14 | Viewed by 4195

Abstract

Despite significant advances in cancer therapy over the years, its complex pathological process still represents a major health challenge when seeking effective treatment and improved healthcare. With the advent of nanotechnologies, nanomedicine-based cancer therapy has been widely explored as a promising technology able [...] Read more.

Despite significant advances in cancer therapy over the years, its complex pathological process still represents a major health challenge when seeking effective treatment and improved healthcare. With the advent of nanotechnologies, nanomedicine-based cancer therapy has been widely explored as a promising technology able to handle the requirements of the clinical sector. Superparamagnetic iron oxide nanoparticles (SPION) have been at the forefront of nanotechnology development since the mid-1990s, thanks to their former role as contrast agents for magnetic resonance imaging. Though their use as MRI probes has been discontinued due to an unfavorable cost/benefit ratio, several innovative applications as therapeutic tools have prompted a renewal of interest. The unique characteristics of SPION, i.e., their magnetic properties enabling specific response when submitted to high frequency (magnetic hyperthermia) or low frequency (magneto-mechanical therapy) alternating magnetic field, and their ability to generate reactive oxygen species (either intrinsically or when activated using various stimuli), make them particularly adapted for cancer therapy. This review provides a comprehensive description of the fundamental aspects of SPION formulation and highlights various recent approaches regarding in vivo applications in the field of cancer therapy. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials – a Promising Approach in Cancer Therapy)

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Other

Jump to: Research, Review

16 pages, 2010 KiB

Open AccessSystematic Review

Radiolabeled Dendrimer Coated Nanoparticles for Radionuclide Imaging and Therapy: A Systematic Review

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Miriam Conte

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Maria Silvia De Feo

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Marko Magdi Abdou Sidrak

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Giuseppe De Vincentis

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Viviana Frantellizzi

Pharmaceutics 2023, 15(3), 867; https://doi.org/10.3390/pharmaceutics15030867 - 07 Mar 2023

Viewed by 904

Abstract

Background: Dendrimers are nanoscale-size polymers with a globular structure. They are composed of an internal core and branching dendrons with surface active groups which can be functionalized for medical applications. Different complexes have been developed for imaging and therapeutic purposes. This systematic review [...] Read more.

Background: Dendrimers are nanoscale-size polymers with a globular structure. They are composed of an internal core and branching dendrons with surface active groups which can be functionalized for medical applications. Different complexes have been developed for imaging and therapeutic purposes. This systematic review aims to summarize the development of newer dendrimers for oncological applications in nuclear medicine. Methods: An online literature search was conducted on Pubmed, Scopus, Medline, Cochrane Library, and Web Of Science databases selecting published studies from January 1999 to December 2022. The accepted studies considered the synthesis of dendrimer complexes for oncological nuclear medicine imaging and therapy. Results: 111 articles were identified; 69 articles were excluded because they did not satisfy the selection criteria. Thus, nine duplicate records were removed. The remaining 33 articles were included and selected for quality assessment. Conclusion: Nanomedicine has led researchers to create novel nanocarriers with high affinity for the target. Dendrimers represent feasible imaging probes and therapeutic agents since, through the functionalization of external chemical groups and thanks to the possibility to carry pharmaceuticals, it can be possible to exploit different therapeutic strategies and develop a useful weapon for oncological treatments. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials – a Promising Approach in Cancer Therapy)

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