Editorial

5 pages, 183 KiB

Open AccessEditorial

Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery

by Constantin Mihai Lucaciu

Pharmaceutics 2024, 16(2), 263; https://doi.org/10.3390/pharmaceutics16020263 - 11 Feb 2024

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In recent years, nanomedicine has experienced remarkable advancements, due to the development of new nanomaterials with outstanding properties that have demonstrated significant advantages over traditional medicines [...] Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

Research

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22 pages, 5738 KiB

Open AccessArticle

Field-Induced Agglomerations of Polyethylene-Glycol-Functionalized Nanoclusters: Rheological Behaviour and Optical Microscopy

by Sandor I. Bernad, Vlad Socoliuc, Izabell Craciunescu, Rodica Turcu and Elena S. Bernad

Pharmaceutics 2023, 15(11), 2612; https://doi.org/10.3390/pharmaceutics15112612 - 10 Nov 2023

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Abstract

This research aims to investigate the agglomeration processes of magnetoresponsive functionalized nanocluster suspensions in a magnetic field, as well as how these structures impact the behaviour of these suspensions in biomedical applications. The synthesis, shape, colloidal stability, and magnetic characteristics of PEG-functionalized nanoclusters [...] Read more.

This research aims to investigate the agglomeration processes of magnetoresponsive functionalized nanocluster suspensions in a magnetic field, as well as how these structures impact the behaviour of these suspensions in biomedical applications. The synthesis, shape, colloidal stability, and magnetic characteristics of PEG-functionalized nanoclusters are described in this paper. Experiments using TEM, XPS, dynamic light scattering (DLS), VSM, and optical microscopy were performed to study chain-like agglomeration production and its influence on colloidal behaviour in physiologically relevant suspensions. The applied magnetic field aligns the magnetic moments of the nanoclusters. It provides an attraction between neighbouring particles, resulting in the formation of chains, linear aggregates, or agglomerates of clusters aligned along the applied field direction. Optical microscopy has been used to observe the creation of these aligned linear formations. The design of chain-like structures can cause considerable changes in the characteristics of ferrofluids, ranging from rheological differences to colloidal stability changes. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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15 pages, 3741 KiB

Open AccessArticle

Microfluidic Synthesis of Magnetite Nanoparticles for the Controlled Release of Antibiotics

by Cristina Chircov, Iulia Alexandra Dumitru, Bogdan Stefan Vasile, Ovidiu-Cristian Oprea, Alina Maria Holban and Roxana Cristina Popescu

Pharmaceutics 2023, 15(9), 2215; https://doi.org/10.3390/pharmaceutics15092215 - 27 Aug 2023

Cited by 1 | Viewed by 1144

Abstract

Magnetite nanoparticles (MNPs) have been intensively studied for biomedical applications, especially as drug delivery systems for the treatment of infections. Additionally, they are characterized by intrinsic antimicrobial properties owing to their capacity to disrupt or penetrate the microbial cell wall and induce cell [...] Read more.

Magnetite nanoparticles (MNPs) have been intensively studied for biomedical applications, especially as drug delivery systems for the treatment of infections. Additionally, they are characterized by intrinsic antimicrobial properties owing to their capacity to disrupt or penetrate the microbial cell wall and induce cell death. However, the current focus has shifted towards increasing the control of the synthesis reaction to ensure more uniform nanoparticle sizes and shapes. In this context, microfluidics has emerged as a potential candidate method for the controlled synthesis of nanoparticles. Thus, the aim of the present study was to obtain a series of antibiotic-loaded MNPs through a microfluidic device. The structural properties of the nanoparticles were investigated through X-ray diffraction (XRD) and, selected area electron diffraction (SAED), the morphology was evaluated through transmission electron microscopy (TEM) and high-resolution TEM (HR-TEM), the antibiotic loading was assessed through Fourier-transform infrared spectroscopy (FT-IR) and, and thermogravimetry and differential scanning calorimetry (TG-DSC) analyses, and. the release profiles of both antibiotics was determined through UV-Vis spectroscopy. The biocompatibility of the nanoparticles was assessed through the MTT assay on a BJ cell line, while the antimicrobial properties were investigated against the S. aureus, P. aeruginosa, and C. albicans strains. Results proved considerable uniformity of the antibiotic-containing nanoparticles, good biocompatibility, and promising antimicrobial activity. Therefore, this study represents a step forward towards the microfluidic development of highly effective nanostructured systems for antimicrobial therapies. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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20 pages, 20426 KiB

Open AccessArticle

High Efficacy on the Death of Breast Cancer Cells Using SPMHT with Magnetite Cyclodextrins Nanobioconjugates

by Costica Caizer, Isabela Simona Caizer-Gaitan, Claudia Geanina Watz, Cristina Adriana Dehelean, Tiberiu Bratu and Codruța Soica

Pharmaceutics 2023, 15(4), 1145; https://doi.org/10.3390/pharmaceutics15041145 - 04 Apr 2023

Cited by 2 | Viewed by 1268

Abstract

In this study, we present the experimental results obtained in vitro on the human breast adenocarcinoma cell line (MCF-7) by applying superparamagnetic hyperthermia (SPMHT) using novel Fe₃O₄-PAA–(HP-γ-CDs) (PAA is polyacrylic acid and HP-γ-CDs is hydroxypropyl gamma-cyclodextrins) nanobioconjugates previously obtained [...] Read more.

In this study, we present the experimental results obtained in vitro on the human breast adenocarcinoma cell line (MCF-7) by applying superparamagnetic hyperthermia (SPMHT) using novel Fe₃O₄-PAA–(HP-γ-CDs) (PAA is polyacrylic acid and HP-γ-CDs is hydroxypropyl gamma-cyclodextrins) nanobioconjugates previously obtained by us. In the in vitro SPMHT experiments, we used concentrations of 1, 5 and 10 mg/mL of Fe₃O₄ ferrimagnetic nanoparticles from Fe₃O₄-PAA–(HP-γ-CDs) nanobioconjugates suspended in culture media containing 1 × 10⁵ MCF-7 human breast adenocarcinoma cells. The harmonic alternating magnetic field used in the in vitro experiments that did not affect cell viability was found to be optimal in the range of 160–378 Gs and at a frequency of 312.2 kHz. The appropriate duration of the therapy was 30 min. After applying SPMHT with these nanobioconjugates under the above conditions, MCF-7 cancer cells died out in a very high percentage, of until 95.11%. Moreover, we studied the field up to which magnetic hyperthermia can be safely applied without cellular toxicity, and found a new upper biological limit H × f ~9.5 × 10⁹ A/m⋅Hz (H is the amplitude and f is the frequency of the alternating magnetic field) to safely apply the magnetic field in vitro in the case of MCF-7 cells; the value was twice as high compared to the currently known value. This is a major advantage for magnetic hyperthermia in vitro and in vivo, because it allows one to achieve a therapy temperature of 43 °C safely in a much shorter time without affecting healthy cells. At the same time, using the new biological limit for a magnetic field, the concentration of magnetic nanoparticles in magnetic hyperthermia can be greatly reduced, obtaining the same hyperthermic effect, while at the same time, reducing cellular toxicity. This new limit of the magnetic field was tested by us in vitro with very good results, without the cell viability decreasing below ~90%. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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19 pages, 4033 KiB

Open AccessArticle

Multimodal Radiobioconjugates of Magnetic Nanoparticles Labeled with ⁴⁴Sc and ⁴⁷Sc for Theranostic Application

by Perihan Ünak, Volkan Yasakçı, Elif Tutun, K. Buşra Karatay, Rafał Walczak, Kamil Wawrowicz, Kinga Żelechowska-Matysiak, Agnieszka Majkowska-Pilip and Aleksander Bilewicz

Pharmaceutics 2023, 15(3), 850; https://doi.org/10.3390/pharmaceutics15030850 - 05 Mar 2023

Cited by 3 | Viewed by 1918

Abstract

This study was performed to synthesize multimodal radiopharmaceutical designed for the diagnosis and treatment of prostate cancer. To achieve this goal, superparamagnetic iron oxide (SPIO) nanoparticles were used as a platform for targeting molecule (PSMA-617) and for complexation of two scandium radionuclides, ⁴⁴ [...] Read more.

This study was performed to synthesize multimodal radiopharmaceutical designed for the diagnosis and treatment of prostate cancer. To achieve this goal, superparamagnetic iron oxide (SPIO) nanoparticles were used as a platform for targeting molecule (PSMA-617) and for complexation of two scandium radionuclides, ⁴⁴Sc for PET imaging and ⁴⁷Sc for radionuclide therapy. TEM and XPS images showed that the Fe₃O₄ NPs have a uniform cubic shape and a size from 38 to 50 nm. The Fe₃O₄ core are surrounded by SiO₂ and an organic layer. The saturation magnetization of the SPION core was 60 emu/g. However, coating the SPIONs with silica and polyglycerol reduces the magnetization significantly. The obtained bioconjugates were labeled with ⁴⁴Sc and ⁴⁷Sc, with a yield higher than 97%. The radiobioconjugate exhibited high affinity and cytotoxicity toward the human prostate cancer LNCaP (PSMA+) cell line, much higher than for PC-3 (PSMA-) cells. High cytotoxicity of the radiobioconjugate was confirmed by radiotoxicity studies on LNCaP 3D spheroids. In addition, the magnetic properties of the radiobioconjugate should allow for its use in guide drug delivery driven by magnetic field gradient. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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19 pages, 3194 KiB

Open AccessArticle

Paclitaxel-Loaded Lipid-Coated Magnetic Nanoparticles for Dual Chemo-Magnetic Hyperthermia Therapy of Melanoma

by Relton R. Oliveira, Emílio R. Cintra, Ailton A. Sousa-Junior, Larissa C. Moreira, Artur C. G. da Silva, Ana Luiza R. de Souza, Marize C. Valadares, Marcus S. Carrião, Andris F. Bakuzis and Eliana M. Lima

Pharmaceutics 2023, 15(3), 818; https://doi.org/10.3390/pharmaceutics15030818 - 02 Mar 2023

Cited by 6 | Viewed by 2061

Abstract

Melanoma is the most aggressive and metastasis-prone form of skin cancer. Conventional therapies include chemotherapeutic agents, either as small molecules or carried by FDA-approved nanostructures. However, systemic toxicity and side effects still remain as major drawbacks. With the advancement of nanomedicine, new delivery [...] Read more.

Melanoma is the most aggressive and metastasis-prone form of skin cancer. Conventional therapies include chemotherapeutic agents, either as small molecules or carried by FDA-approved nanostructures. However, systemic toxicity and side effects still remain as major drawbacks. With the advancement of nanomedicine, new delivery strategies emerge at a regular pace, aiming to overcome these challenges. Stimulus-responsive drug delivery systems might considerably reduce systemic toxicity and side-effects by limiting drug release to the affected area. Herein, we report the development of paclitaxel-loaded lipid-coated manganese ferrite magnetic nanoparticles (PTX-LMNP) as magnetosomes synthetic analogs, envisaging the combined chemo-magnetic hyperthermia treatment of melanoma. PTX-LMNP physicochemical properties were verified, including their shape, size, crystallinity, FTIR spectrum, magnetization profile, and temperature profile under magnetic hyperthermia (MHT). Their diffusion in porcine ear skin (a model for human skin) was investigated after intradermal administration via fluorescence microscopy. Cumulative PTX release kinetics under different temperatures, either preceded or not by MHT, were assessed. Intrinsic cytotoxicity against B16F10 cells was determined via neutral red uptake assay after 48 h of incubation (long-term assay), as well as B16F10 cells viability after 1 h of incubation (short-term assay), followed by MHT. PTX-LMNP-mediated MHT triggers PTX release, allowing its thermal-modulated local delivery to diseased sites, within short timeframes. Moreover, half-maximal PTX inhibitory concentration (IC₅₀) could be significantly reduced relatively to free PTX (142,500×) and Taxol^® (340×). Therefore, the dual chemo-MHT therapy mediated by intratumorally injected PTX-LMNP stands out as a promising alternative to efficiently deliver PTX to melanoma cells, consequently reducing systemic side effects commonly associated with conventional chemotherapies. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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18 pages, 3546 KiB

Open AccessArticle

Doxorubicin Loaded Thermosensitive Magneto-Liposomes Obtained by a Gel Hydration Technique: Characterization and In Vitro Magneto-Chemotherapeutic Effect Assessment

by Stefan Nitica, Ionel Fizesan, Roxana Dudric, Felicia Loghin, Constantin Mihai Lucaciu and Cristian Iacovita

Pharmaceutics 2022, 14(11), 2501; https://doi.org/10.3390/pharmaceutics14112501 - 18 Nov 2022

Cited by 7 | Viewed by 1626

Abstract

The combination of magnetic hyperthermia with chemotherapy is considered a promising strategy in cancer therapy due to the synergy between the high temperatures and the chemotherapeutic effects, which can be further developed for targeted and remote-controlled drug release. In this paper we report [...] Read more.

The combination of magnetic hyperthermia with chemotherapy is considered a promising strategy in cancer therapy due to the synergy between the high temperatures and the chemotherapeutic effects, which can be further developed for targeted and remote-controlled drug release. In this paper we report a simple, rapid, and reproducible method for the preparation of thermosensitive magnetoliposomes (TsMLs) loaded with doxorubicin (DOX), consisting of a lipidic gel formation from a previously obtained water-in-oil microemulsion with fine aqueous droplets containing magnetic nanoparticles (MNPs) dispersed in an organic solution of thermosensitive lipids (transition temperature of ~43 °C), followed by the gel hydration with an aqueous solution of DOX. The obtained thermosensitive magnetoliposomes (TsMLs) were around 300 nm in diameter and exhibited 40% DOX incorporation efficiency. The most suitable MNPs to incorporate into the liposomal aqueous lumen were Zn ferrites, with a very low coercive field at 300 K (7 kA/m) close to the superparamagnetic regime, exhibiting a maximum absorption rate (SAR) of 1130 W/gFe when dispersed in water and 635 W/gFe when confined inside TsMLs. No toxicity of Zn ferrite MNPs or of TsMLs was noticed against the A459 cancer cell line after 48 h incubation over the tested concentration range. The passive release of DOX from the TsMLs after 48h incubation induced a toxicity starting with a dosage level of 62.5 ug/cm². Below this threshold, the subsequent exposure to an alternating magnetic field (20–30 kA/m, 355 kHz) for 30 min drastically reduced the viability of the A459 cells due to the release of incorporated DOX. Our results strongly suggest that TsMLs represent a viable strategy for anticancer therapies using the magnetic field-controlled release of DOX. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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21 pages, 4475 KiB

Open AccessArticle

The Anti-Obesity Potential of Superparamagnetic Iron Oxide Nanoparticles against High-Fat Diet-Induced Obesity in Rats: Possible Involvement of Mitochondrial Biogenesis in the Adipose Tissues

by Aisha H. A. Alsenousy, Rasha A. El-Tahan, Nesma A. Ghazal, Rafael Piñol, Angel Millán, Lamiaa M. A. Ali and Maher A. Kamel

Pharmaceutics 2022, 14(10), 2134; https://doi.org/10.3390/pharmaceutics14102134 - 08 Oct 2022

Cited by 3 | Viewed by 2129

Abstract

Background: Obesity is a pandemic disease that is rapidly growing into a serious health problem and has economic impact on healthcare systems. This bleak image has elicited creative responses, and nanotechnology is a promising approach in obesity treatment. This study aimed to investigate [...] Read more.

Background: Obesity is a pandemic disease that is rapidly growing into a serious health problem and has economic impact on healthcare systems. This bleak image has elicited creative responses, and nanotechnology is a promising approach in obesity treatment. This study aimed to investigate the anti-obesity effect of superparamagnetic iron oxide nanoparticles (SPIONs) on a high-fat-diet rat model of obesity and compared their effect to a traditional anti-obesity drug (orlistat). Methods: The obese rats were treated daily with orlistat and/or SPIONs once per week for 8 weeks. At the end of the experiment, blood samples were collected for biochemical assays. Then, the animals were sacrificed to obtain white adipose tissues (WAT) and brown adipose tissues (BAT) for assessment of the expression of thermogenic genes and mitochondrial DNA copy number (mtDNA-CN). Results: For the first time, we reported promising ameliorating effects of SPIONs treatments against weight gain, hyperglycemia, adiponectin, leptin, and dyslipidemia in obese rats. At the molecular level, surprisingly, SPIONs treatments markedly corrected the disturbed expression and protein content of inflammatory markers and parameters controlling mitochondrial biogenesis and functions in BAT and WAT. Conclusions: SPIONs have a powerful anti-obesity effect by acting as an inducer of WAT browning and activator of BAT functions. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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Review

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37 pages, 5906 KiB

Open AccessReview

Recent Advances in the Development of Drug Delivery Applications of Magnetic Nanomaterials

by Alexandra Pusta, Mihaela Tertis, Izabell Crăciunescu, Rodica Turcu, Simona Mirel and Cecilia Cristea

Pharmaceutics 2023, 15(7), 1872; https://doi.org/10.3390/pharmaceutics15071872 - 03 Jul 2023

Cited by 9 | Viewed by 2019

Abstract

With the predicted rise in the incidence of cancer, there is an ever-growing need for new cancer treatment strategies. Recently, magnetic nanoparticles have stood out as promising nanostructures for imaging and drug delivery systems as they possess unique properties. Moreover, magnetic nanomaterials functionalized [...] Read more.

With the predicted rise in the incidence of cancer, there is an ever-growing need for new cancer treatment strategies. Recently, magnetic nanoparticles have stood out as promising nanostructures for imaging and drug delivery systems as they possess unique properties. Moreover, magnetic nanomaterials functionalized with other compounds can lead to multicomponent nanoparticles with innovative structures and synergetic performance. The incorporation of chemotherapeutic drugs or RNA in magnetic drug delivery systems represents a promising alternative that can increase efficiency and reduce the side effects of anticancer therapy. This review presents a critical overview of the recent literature concerning the advancements in the field of magnetic nanoparticles used in drug delivery, with a focus on their classification, characteristics, synthesis and functionalization methods, limitations, and examples of magnetic drug delivery systems incorporating chemotherapeutics or RNA. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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34 pages, 4709 KiB

Open AccessReview

Bioimaging Probes Based on Magneto-Fluorescent Nanoparticles

by Sayan Ganguly and Shlomo Margel

Pharmaceutics 2023, 15(2), 686; https://doi.org/10.3390/pharmaceutics15020686 - 17 Feb 2023

Cited by 10 | Viewed by 2967

Abstract

Novel nanomaterials are of interest in biology, medicine, and imaging applications. Multimodal fluorescent-magnetic nanoparticles demand special attention because they have the potential to be employed as diagnostic and medication-delivery tools, which, in turn, might make it easier to diagnose and treat cancer, as [...] Read more.

Novel nanomaterials are of interest in biology, medicine, and imaging applications. Multimodal fluorescent-magnetic nanoparticles demand special attention because they have the potential to be employed as diagnostic and medication-delivery tools, which, in turn, might make it easier to diagnose and treat cancer, as well as a wide variety of other disorders. The most recent advancements in the development of magneto-fluorescent nanocomposites and their applications in the biomedical field are the primary focus of this review. We describe the most current developments in synthetic methodologies and methods for the fabrication of magneto-fluorescent nanocomposites. The primary applications of multimodal magneto-fluorescent nanoparticles in biomedicine, including biological imaging, cancer treatment, and drug administration, are covered in this article, and an overview of the future possibilities for these technologies is provided. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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24 pages, 4444 KiB

Open AccessReview

Iron-Based Ceramic Composite Nanomaterials for Magnetic Fluid Hyperthermia and Drug Delivery

by Ming-Hsien Chan, Chien-Hsiu Li, Yu-Chan Chang and Michael Hsiao

Pharmaceutics 2022, 14(12), 2584; https://doi.org/10.3390/pharmaceutics14122584 - 24 Nov 2022

Cited by 10 | Viewed by 2645

Abstract

Because of the unique physicochemical properties of magnetic iron-based nanoparticles, such as superparamagnetism, high saturation magnetization, and high effective surface area, they have been applied in biomedical fields such as diagnostic imaging, disease treatment, and biochemical separation. Iron-based nanoparticles have been used in [...] Read more.

Because of the unique physicochemical properties of magnetic iron-based nanoparticles, such as superparamagnetism, high saturation magnetization, and high effective surface area, they have been applied in biomedical fields such as diagnostic imaging, disease treatment, and biochemical separation. Iron-based nanoparticles have been used in magnetic resonance imaging (MRI) to produce clearer and more detailed images, and they have therapeutic applications in magnetic fluid hyperthermia (MFH). In recent years, researchers have used clay minerals, such as ceramic materials with iron-based nanoparticles, to construct nanocomposite materials with enhanced saturation, magnetization, and thermal effects. Owing to their unique structure and large specific surface area, iron-based nanoparticles can be homogenized by adding different proportions of ceramic minerals before and after modification to enhance saturation magnetization. In this review, we assess the potential to improve the magnetic properties of iron-based nanoparticles and in the preparation of multifunctional composite materials through their combination with ceramic materials. We demonstrate the potential of ferromagnetic enhancement and multifunctional composite materials for MRI diagnosis, drug delivery, MFH therapy, and cellular imaging applications. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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Other

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16 pages, 1422 KiB

Open AccessSystematic Review

Nanomedicine and Hyperthermia for the Treatment of Gastrointestinal Cancer: A Systematic Review

by Lidia Gago, Francisco Quiñonero, Gloria Perazzoli, Consolación Melguizo, Jose Prados, Raul Ortiz and Laura Cabeza

Pharmaceutics 2023, 15(7), 1958; https://doi.org/10.3390/pharmaceutics15071958 - 15 Jul 2023

Cited by 2 | Viewed by 1425

Abstract

The incidence of gastrointestinal cancers has increased in recent years. Current treatments present numerous challenges, including drug resistance, non-specificity, and severe side effects, needing the exploration of new therapeutic strategies. One promising avenue is the use of magnetic nanoparticles, which have gained considerable [...] Read more.

The incidence of gastrointestinal cancers has increased in recent years. Current treatments present numerous challenges, including drug resistance, non-specificity, and severe side effects, needing the exploration of new therapeutic strategies. One promising avenue is the use of magnetic nanoparticles, which have gained considerable interest due to their ability to generate heat in tumor regions upon the application of an external alternating magnetic field, a process known as hyperthermia. This review conducted a systematic search of in vitro and in vivo studies published in the last decade that employ hyperthermia therapy mediated by magnetic nanoparticles for treating gastrointestinal cancers. After applying various inclusion and exclusion criteria (studies in the last 10 years where hyperthermia using alternative magnetic field is applied), a total of 40 articles were analyzed. The results revealed that iron oxide is the preferred material for magnetism generation in the nanoparticles, and colorectal cancer is the most studied gastrointestinal cancer. Interestingly, novel therapies employing nanoparticles loaded with chemotherapeutic drugs in combination with magnetic hyperthermia demonstrated an excellent antitumor effect. In conclusion, hyperthermia treatments mediated by magnetic nanoparticles appear to be an effective approach for the treatment of gastrointestinal cancers, offering advantages over traditional therapies. Full article

(This article belongs to the Special Issue Magnetic Nanomaterials for Hyperthermia-Based Therapy, Imaging, and Drug Delivery)

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