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Pharmaceutics
Special Issues
Magnetic Nanoparticles for Bone Regeneration and Cancer Therapy
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Magnetic Nanoparticles for Bone Regeneration and Cancer Therapy

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 7859

Special Issue Editors

Prof. Dr. Fernando J. Monteiro

E-Mail Website
Guest Editor
I3S—Instituto de Investigação e Inovação em Saúde, FEUP (Faculdade de Engenharia da Universidade do Porto), Porto, Portugal
Interests: magnetic nanoparticles; cancer; bone regeneration
Special Issues, Collections and Topics in MDPI journals
Dr. Marta Laranjeira

E-Mail Website
Guest Editor
I3S—Instituto de Investigação e Inovação em Saúde, Porto, Portugal
Interests: magnetic nanoparticles; cancer; bone regeneration

Special Issue Information

Dear Colleagues,

Nanoparticles magneto-responsive are recently studied and already applied in medicine for magnetic resonance imaging, drug delivery systems, tissue regeneration, cancer diagnosis and treatment, extraction of biomolecules and lab-on-a-chip others.

The magnetic nanoparticles have exciting properties such as controllable and uniform size, superparamagnetism and high surface area. They have the remarkable possibility to be controlled from a distance or allow thermal activation when exposed to an alternating magnetic field. For example, therapeutic hyperthermia is a cancer treatment that injects magnetic nanoparticles directly into tumors, and FDA has already approved it. Drug delivery systems can likewise take advantage of magnetism to face its two main challenges: targeting the drug to a specific site and having the ability to control drug release over time. Thus, another possible approach is to implant a magnetic scaffold in the site where the drug must be delivered that will work as a target to attract the magnetic nanoparticles conjugated with the drug and allow the control of their spatial distribution.

Regarding bone tissue regeneration, several in vivo and in vitro studies report osteogenesis improvement after bone or bone cells exposition to a particular intensity of a magnetic field. Even so, the clinical applications of magnetism in bone regeneration are still at a very early stage.

Magnetic materials involve considering numerous parameters, such as their composition, the shape of the material, their preparation process, or the intensity of their magnetic field. It is, therefore, crucial to fully understand how the interactions between nanoparticles and cells work to determine the optimal parameters that enable achieving the best possible response from the biological system.

The safety of using magnetic nanoparticles is still a question to be answered since the information about the effects of exposure to magnetic fields and the presence of the remains of magnetic nanoparticles inside the body are not yet clearly determined. Taking all these questions into account, the primary aim of this Special Issue is to summarise recent research and the state-of-the-art use of magnetic nanoparticles in cancer diagnosis and treatment and bone tissue regeneration.

Prof. Dr. Fernando J. Monteiro
Dr. Marta Laranjeira
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • magnetic nanoparticles
  • magnetic field
  • cancer
  • bone tissue regeneration
  • biomedicine

Published Papers (5 papers)

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Research

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17 pages, 3999 KiB  
Article
Remote Activation of Mechanotransduction via Integrin Alpha-5 via Aptamer-Conjugated Magnetic Nanoparticles Promotes Osteogenesis
by Hadi Hajiali, Michael Rotherham and Alicia J. El Haj
Pharmaceutics 2024, 16(1), 21; https://doi.org/10.3390/pharmaceutics16010021 - 22 Dec 2023
Cited by 1 | Viewed by 897
Abstract
Bone regeneration and repair are complex processes in the adult skeleton, and current research has focused on understanding and controlling these processes. Magnetic nanoparticle (MNP)-based platforms have shown potential in tissue engineering and regenerative medicine through the use of magnetic nanomaterials combined with [...] Read more.
Bone regeneration and repair are complex processes in the adult skeleton, and current research has focused on understanding and controlling these processes. Magnetic nanoparticle (MNP)-based platforms have shown potential in tissue engineering and regenerative medicine through the use of magnetic nanomaterials combined with remotely applied dynamic fields. Previous studies have demonstrated the ability of MNP-induced mechanoactivation to trigger downstream signaling and promote new bone formation. In this study, we aimed to compare the osteogenic induction achieved using the mechanoreceptor targets, Piezo1, Fzd1, Fzd2, and integrin alpha-5. We compared the binding efficacy of different types of agonists (antibodies vs. aptamers) to these receptors. Moreover, we optimized the aptamer concentration (2.5, 5, and 10 μg/mg) for the selected receptor to determine the optimum concentration for promoting bone formation. Our data demonstrated that the mechanoactivation of integrins (CD49e) significantly upregulated the RUNX2 and LEF1 genes compared to other selected receptors. Furthermore, comparing the mechanoactivation of cells using MNPs conjugated with CD49e antibodies and aptamers revealed that MNP–aptamers significantly enhanced the upregulation of LEF1 genes. This suggests that aptamer-mediated mechanoactivation is a promising alternative to antibody-mediated activation. Finally, our results showed that the concentration of the aptamer loaded onto the MNPs strongly influenced the mechanoactivation of the cells. These findings provide valuable insights into the use of MNP platforms for bone regeneration and highlight the potential of aptamers in promoting signaling pathways related to bone formation. The novelty of our study lies in elucidating the unique advantages of aptamers in mediating mechanoactivation, presenting a promising avenue for advancing bone regenerative strategies. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles for Bone Regeneration and Cancer Therapy)
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11 pages, 2255 KiB  
Article
Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors
by Luis Daniel Terrazas-Armendáriz, Cynthia Aracely Alvizo-Báez, Itza Eloisa Luna-Cruz, Becky Annette Hernández-González, Ashanti Concepción Uscanga-Palomeque, Mitchel Abraham Ruiz-Robles, Eduardo Gerardo Pérez Tijerina, Cristina Rodríguez-Padilla, Reyes Tamez-Guerra and Juan Manuel Alcocer-González
Pharmaceutics 2023, 15(9), 2232; https://doi.org/10.3390/pharmaceutics15092232 - 29 Aug 2023
Viewed by 826
Abstract
Cancer is a disease that causes millions of deaths per year worldwide because conventional treatments have disadvantages such as unspecific tumor selectivity and unwanted toxicity. Most human solid tumors present hypoxic microenvironments and this promotes multidrug resistance. In this study, we present “Magnetogene [...] Read more.
Cancer is a disease that causes millions of deaths per year worldwide because conventional treatments have disadvantages such as unspecific tumor selectivity and unwanted toxicity. Most human solid tumors present hypoxic microenvironments and this promotes multidrug resistance. In this study, we present “Magnetogene nanoparticle vector” which takes advantage of the hypoxic microenvironment of solid tumors to increase selective gene expression in tumor cells and reduce unwanted toxicity in healthy cells; this vector was guided by a magnet to the tumor tissue. Magnetic nanoparticles (MNPs), chitosan (CS), and the pHRE-Luc plasmid with a hypoxia-inducible promoter were used to synthesize the vector called “Magnetogene nanoparticles” by ionic gelation. The hypoxic functionality of Magnetogene vector nanoparticles was confirmed in the B16F10 cell line by measuring the expression of the luciferase reporter gene under hypoxic and normoxic conditions. Also, the efficiency of the Magnetogene vector was confirmed in vivo. Magnetogene was administered by intravenous injection (IV) in the tail vein and directed through an external magnetic field at the site of tumor growth in C57Bl/6 mice. A Magnetogene vector with a size of 50 to 70 nm was directed and retained at the tumor area and gene expression was higher at the tumor site than in the others tissues, confirming the selectivity of this vector towards hypoxic tumor areas. This nanosystem, that we called the “Magnetogene vector” for systemic delivery and specific gene expression in hypoxic tumors controlled by an external magnetic designed to target hypoxic regions of tumors, can be used for cancer-specific gene therapies. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles for Bone Regeneration and Cancer Therapy)
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26 pages, 5412 KiB  
Article
Macrophage Reprogramming via the Modulation of Unfolded Protein Response with siRNA-Loaded Magnetic Nanoparticles in a TAM-like Experimental Model
by Annarita D’Urso, Francesca Oltolina, Chiara Borsotti, Maria Prat, Donato Colangelo and Antonia Follenzi
Pharmaceutics 2023, 15(6), 1711; https://doi.org/10.3390/pharmaceutics15061711 - 12 Jun 2023
Cited by 1 | Viewed by 1362
Abstract
New therapeutic strategies are required in cancer therapy. Considering the prominent role of tumor-associated macrophages (TAMs) in the development and progression of cancer, the re-education of TAMs in the tumor microenvironment (TME) could represent a potential approach for cancer immunotherapy. TAMs display an [...] Read more.
New therapeutic strategies are required in cancer therapy. Considering the prominent role of tumor-associated macrophages (TAMs) in the development and progression of cancer, the re-education of TAMs in the tumor microenvironment (TME) could represent a potential approach for cancer immunotherapy. TAMs display an irregular unfolded protein response (UPR) in their endoplasmic reticulum (ER) to endure environmental stress and ensure anti-cancer immunity. Therefore, nanotechnology could be an attractive tool to modulate the UPR in TAMs, providing an alternative strategy for TAM-targeted repolarization therapy. Herein, we developed and tested polydopamine-coupled magnetite nanoparticles (PDA-MNPs) functionalized with small interfering RNAs (siRNA) to downregulate the protein kinase R (PKR)-like ER kinase (PERK) expression in TAM-like macrophages derived from murine peritoneal exudate (PEMs). After the evaluation of the cytocompatibility, the cellular uptake, and the gene silencing efficiency of PDA-MNPs/siPERK in PEMs, we analyzed their ability to re-polarize in vitro these macrophages from M2 to the M1 inflammatory anti-tumor phenotype. Our results indicate that PDA-MNPs, with their magnetic and immunomodulator features, are cytocompatible and able to re-educate TAMs toward the M1 phenotype by PERK inhibition, a UPR effector contributing to TAM metabolic adaptation. These findings can provide a novel strategy for the development of new tumor immunotherapies in vivo. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles for Bone Regeneration and Cancer Therapy)
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Review

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22 pages, 4315 KiB  
Review
Graphene-Based Nanomaterials for Photothermal Therapy in Cancer Treatment
by Daniela F. Báez
Pharmaceutics 2023, 15(9), 2286; https://doi.org/10.3390/pharmaceutics15092286 - 06 Sep 2023
Cited by 4 | Viewed by 1624
Abstract
Graphene-based nanomaterials (GBNMs), specifically graphene oxide (GO) and reduced graphene oxide (rGO), have shown great potential in cancer therapy owing to their physicochemical properties. As GO and rGO strongly absorb light in the near-infrared (NIR) region, they are useful in photothermal therapy (PTT) [...] Read more.
Graphene-based nanomaterials (GBNMs), specifically graphene oxide (GO) and reduced graphene oxide (rGO), have shown great potential in cancer therapy owing to their physicochemical properties. As GO and rGO strongly absorb light in the near-infrared (NIR) region, they are useful in photothermal therapy (PTT) for cancer treatment. However, despite the structural similarities of GO and rGO, they exhibit different influences on anticancer treatment due to their different photothermal capacities. In this review, various characterization techniques used to compare the structural features of GO and rGO are first outlined. Then, a comprehensive summary and discussion of the applicability of GBNMs in the context of PTT for diverse cancer types are presented. This discussion includes the integration of PTT with secondary therapeutic strategies, with a particular focus on the photothermal capacity achieved through near-infrared irradiation parameters and the modifications implemented. Furthermore, a dedicated section is devoted to studies on hybrid magnetic-GBNMs. Finally, the challenges and prospects associated with the utilization of GBNM in PTT, with a primary emphasis on the potential for clinical translation, are addressed. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles for Bone Regeneration and Cancer Therapy)
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20 pages, 1030 KiB  
Review
Magnetic Bone Tissue Engineering: Reviewing the Effects of Magnetic Stimulation on Bone Regeneration and Angiogenesis
by Tiago P. Ribeiro, Miguel Flores, Sara Madureira, Francesca Zanotto, Fernando J. Monteiro and Marta S. Laranjeira
Pharmaceutics 2023, 15(4), 1045; https://doi.org/10.3390/pharmaceutics15041045 - 23 Mar 2023
Cited by 7 | Viewed by 2429
Abstract
Bone tissue engineering emerged as a solution to treat critical bone defects, aiding in tissue regeneration and implant integration. Mainly, this field is based on the development of scaffolds and coatings that stimulate cells to proliferate and differentiate in order to create a [...] Read more.
Bone tissue engineering emerged as a solution to treat critical bone defects, aiding in tissue regeneration and implant integration. Mainly, this field is based on the development of scaffolds and coatings that stimulate cells to proliferate and differentiate in order to create a biologically active bone substitute. In terms of materials, several polymeric and ceramic scaffolds have been developed and their properties tailored with the objective to promote bone regeneration. These scaffolds usually provide physical support for cells to adhere, while giving chemical and physical stimuli for cell proliferation and differentiation. Among the different cells that compose the bone tissue, osteoblasts, osteoclasts, stem cells, and endothelial cells are the most relevant in bone remodeling and regeneration, being the most studied in terms of scaffold–cell interactions. Besides the intrinsic properties of bone substitutes, magnetic stimulation has been recently described as an aid in bone regeneration. External magnetic stimulation induced additional physical stimulation in cells, which in combination with different scaffolds, can lead to a faster regeneration. This can be achieved by external magnetic fields alone, or by their combination with magnetic materials such as nanoparticles, biocomposites, and coatings. Thus, this review is designed to summarize the studies on magnetic stimulation for bone regeneration. While providing information regarding the effects of magnetic fields on cells involved in bone tissue, this review discusses the advances made regarding the combination of magnetic fields with magnetic nanoparticles, magnetic scaffolds, and coatings and their subsequent influence on cells to reach optimal bone regeneration. In conclusion, several research works suggest that magnetic fields may play a role in regulating the growth of blood vessels, which are critical for tissue healing and regeneration. While more research is needed to fully understand the relationship between magnetism, bone cells, and angiogenesis, these findings promise to develop new therapies and treatments for various conditions, from bone fractures to osteoporosis. Full article
(This article belongs to the Special Issue Magnetic Nanoparticles for Bone Regeneration and Cancer Therapy)
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