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Pharmaceutics
Special Issues
Pharmacotherapy of Glioblastoma – Recent Improvements and Novel Perspectives
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Pharmacotherapy of Glioblastoma – Recent Improvements and Novel Perspectives

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

Deadline for manuscript submissions: closed (30 March 2023) | Viewed by 11654

Special Issue Editors

Dr. Magdalena Kusaczuk

E-Mail Website
Guest Editor
Department of Pharmaceutical Biochemistry, Medical University of Bialystok, 15-222 Bialystok, Poland
Interests: glioblastoma; epigenetics; pharmacology; cancer; cell stress; chaperones
Dr. Monika Naumowicz

E-Mail Website
Co-Guest Editor
Laboratory of Bioelectrochemistry, Department of Physical Chemistry, Faculty of Chemistry, University of Bialystok, 15-245 Bialystok, Poland
Interests: lipid membranes; liposomes; emerging pollutant; toxicology
Special Issues, Collections and Topics in MDPI journals
Dr. Guillermo Velasco

E-Mail Website1 Website2
Co-Guest Editor
Department of Biochemistry and Molecular Biology, School of Biology, Complutense University, and Instituto de Investigaciones Sanitarias San Carlos (IdISSC), 28040 Madrid, Spain
Interests: cannabinoids; glioma; autophagy; tribbles proteins; sphingolipids; cell signaling; anticancer therapies; midkine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Glioblastoma (GBM) is one of the most aggressive forms of cancer, and has a very poor survival rate. Several factors, such as the presence of the blood–brain barrier (which limits the access of drugs to the brain parenchyma), the high molecular and cellular heterogeneity of GBM, the presence within these tumors of a population of cells with stem-like properties, and the difficulties in developing specific targeted therapies, have hindered the development of effective GBM therapies. Remarkably, plasma membrane properties have a high impact on drug–membrane interactions and drug permeability, and therefore should be considered for the design of novel therapeutic approaches against GBM.

Authors are invited to submit original and review articles covering all aspects of emerging pharmacotherapeutic strategies to fight GBM. These include, but are not limited to, pharmaceutical nanotechnology, nanocarriers, immunotherapy, epigenetic modifiers, innovative analytical approaches, and natural-product-based drugs.

Dr. Magdalena Kusaczuk
Dr. Monika Naumowicz
Dr. Guillermo Velasco
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

  • investigational therapies
  • pharmacological epigenetic modifiers
  • targeted therapy
  • nanotechnology
  • natural products
  • immunotherapy
  • resistance to therapy
  • glioma stem-like cells
  • electroanalytical methods
  • liposomes
  • physicochemical phenomena at the membrane surface

Published Papers (4 papers)

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Research

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22 pages, 2883 KiB  
Article
Glioblastoma Multiforme Selective Nanomedicines for Improved Anti-Cancer Treatments
by Jason Thomas Duskey, Arianna Rinaldi, Ilaria Ottonelli, Riccardo Caraffi, Chiara Alessia De Benedictis, Ann Katrin Sauer, Giovanni Tosi, Maria Angela Vandelli, Barbara Ruozi and Andreas Martin Grabrucker
Pharmaceutics 2022, 14(7), 1450; https://doi.org/10.3390/pharmaceutics14071450 - 12 Jul 2022
Cited by 7 | Viewed by 2402
Abstract
Glioblastoma Multiforme (GBM) is a devastating disease with a low survival rate and few efficacious treatment options. The fast growth, late diagnostics, and off-target toxicity of currently used drugs represent major barriers that need to be overcome to provide a viable cure. Nanomedicines [...] Read more.
Glioblastoma Multiforme (GBM) is a devastating disease with a low survival rate and few efficacious treatment options. The fast growth, late diagnostics, and off-target toxicity of currently used drugs represent major barriers that need to be overcome to provide a viable cure. Nanomedicines (NMeds) offer a way to overcome these pitfalls by protecting and loading drugs, increasing blood half-life, and being targetable with specific ligands on their surface. In this study, the FDA-approved polymer poly (lactic-co-glycolic) acid was used to optimise NMeds that were surface modified with a series of potential GBM-specific ligands. The NMeds were fully characterised for their physical and chemical properties, and then in vitro testing was performed to evaluate cell uptake and GBM cell specificity. While all targeted NMeds showed improved uptake, only those decorated with the-cell surface vimentin antibody M08 showed specificity for GBM over healthy cells. Finally, the most promising targeted NMed candidate was loaded with the well-known chemotherapeutic, paclitaxel, to confirm targeting and therapeutic effects in C6 GBM cells. These results demonstrate the importance of using well-optimised NMeds targeted with novel ligands to advance delivery and pharmaceutical effects against diseased cells while minimising the risk for nearby healthy cells. Full article
(This article belongs to the Special Issue Pharmacotherapy of Glioblastoma – Recent Improvements and Novel Perspectives)
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15 pages, 7309 KiB  
Article
Iodine Nanoparticles (Niodx™) for Radiotherapy Enhancement of Glioblastoma and Other Cancers: An NCI Nanotechnology Characterization Laboratory Study
by James F. Hainfeld, Sharif M. Ridwan, Yaroslav Stanishevskiy and Henry M. Smilowitz
Pharmaceutics 2022, 14(3), 508; https://doi.org/10.3390/pharmaceutics14030508 - 25 Feb 2022
Cited by 4 | Viewed by 2310
Abstract
Effective and durable treatment of glioblastoma is an urgent unmet medical need. In this article, we summarize a novel approach of a physical method that enhances the effectiveness of radiotherapy. High atomic number nanoparticles that target brain tumors are intravenously administered. Upon irradiation, [...] Read more.
Effective and durable treatment of glioblastoma is an urgent unmet medical need. In this article, we summarize a novel approach of a physical method that enhances the effectiveness of radiotherapy. High atomic number nanoparticles that target brain tumors are intravenously administered. Upon irradiation, the nanoparticles absorb X-rays creating free radicals, increasing the tumor dose several fold. Radiotherapy of mice with orthotopic human gliomas and human triple negative breast cancers growing in the brain showed significant life extensions when the nanoparticles were included. An extensive study of the properties of the iodine-containing nanoparticle (Niodx) by the Nanotechnology Characterization Laboratory, including sterility, physicochemical characterization, in vitro cytotoxicity, in vivo immunological characterization, and in vivo toxicology, is presented. In summary, the iodine nanoparticle Niodx appears safe and effective for translational studies toward human use. Full article
(This article belongs to the Special Issue Pharmacotherapy of Glioblastoma – Recent Improvements and Novel Perspectives)
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Review

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29 pages, 5866 KiB  
Review
Progress and Viewpoints of Multifunctional Composite Nanomaterials for Glioblastoma Theranostics
by Ming-Hsien Chan, Wen-Tse Huang, Aishwarya Satpathy, Ting-Yi Su, Michael Hsiao and Ru-Shi Liu
Pharmaceutics 2022, 14(2), 456; https://doi.org/10.3390/pharmaceutics14020456 - 21 Feb 2022
Cited by 6 | Viewed by 2646
Abstract
The most common malignant tumor of the brain is glioblastoma multiforme (GBM) in adults. Many patients die shortly after diagnosis, and only 6% of patients survive more than 5 years. Moreover, the current average survival of malignant brain tumors is only about 15 [...] Read more.
The most common malignant tumor of the brain is glioblastoma multiforme (GBM) in adults. Many patients die shortly after diagnosis, and only 6% of patients survive more than 5 years. Moreover, the current average survival of malignant brain tumors is only about 15 months, and the recurrence rate within 2 years is almost 100%. Brain diseases are complicated to treat. The reason for this is that drugs are challenging to deliver to the brain because there is a blood–brain barrier (BBB) protection mechanism in the brain, which only allows water, oxygen, and blood sugar to enter the brain through blood vessels. Other chemicals cannot enter the brain due to their large size or are considered harmful substances. As a result, the efficacy of drugs for treating brain diseases is only about 30%, which cannot satisfy treatment expectations. Therefore, researchers have designed many types of nanoparticles and nanocomposites to fight against the most common malignant tumors in the brain, and they have been successful in animal experiments. This review will discuss the application of various nanocomposites in diagnosing and treating GBM. The topics include (1) the efficient and long-term tracking of brain images (magnetic resonance imaging, MRI, and near-infrared light (NIR)); (2) breaking through BBB for drug delivery; and (3) natural and chemical drugs equipped with nanomaterials. These multifunctional nanoparticles can overcome current difficulties and achieve progressive GBM treatment and diagnosis results. Full article
(This article belongs to the Special Issue Pharmacotherapy of Glioblastoma – Recent Improvements and Novel Perspectives)
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31 pages, 2246 KiB  
Review
Neuroimmunomodulatory Properties of Flavonoids and Derivates: A Potential Action as Adjuvants for the Treatment of Glioblastoma
by Ravena Pereira do Nascimento, Balbino Lino dos Santos, Jéssika Alves Oliveira Amparo, Janaina Ribeiro Pereira Soares, Karina Costa da Silva, Monique Reis Santana, Áurea Maria Alves Nunes Almeida, Victor Diógenes Amaral da Silva, Maria de Fátima Dias Costa, Henning Ulrich, Vivaldo Moura-Neto, Giselle Pinto de Faria Lopes and Silvia Lima Costa
Pharmaceutics 2022, 14(1), 116; https://doi.org/10.3390/pharmaceutics14010116 - 04 Jan 2022
Cited by 9 | Viewed by 3153
Abstract
Glioblastomas (GBMs) are tumors that have a high ability to migrate, invade and proliferate in the healthy tissue, what greatly impairs their treatment. These characteristics are associated with the complex microenvironment, formed by the perivascular niche, which is also composed of several stromal [...] Read more.
Glioblastomas (GBMs) are tumors that have a high ability to migrate, invade and proliferate in the healthy tissue, what greatly impairs their treatment. These characteristics are associated with the complex microenvironment, formed by the perivascular niche, which is also composed of several stromal cells including astrocytes, microglia, fibroblasts, pericytes and endothelial cells, supporting tumor progression. Further microglia and macrophages associated with GBMs infiltrate the tumor. These innate immune cells are meant to participate in tumor surveillance and eradication, but they become compromised by GBM cells and exploited in the process. In this review we discuss the context of the GBM microenvironment together with the actions of flavonoids, which have attracted scientific attention due to their pharmacological properties as possible anti-tumor agents. Flavonoids act on a variety of signaling pathways, counteracting the invasion process. Luteolin and rutin inhibit NFκB activation, reducing IL-6 production. Fisetin promotes tumor apoptosis, while inhibiting ADAM expression, reducing invasion. Naringenin reduces tumor invasion by down-regulating metalloproteinases expression. Apigenin and rutin induce apoptosis in C6 cells increasing TNFα, while decreasing IL-10 production, denoting a shift from the immunosuppressive Th2 to the Th1 profile. Overall, flavonoids should be further exploited for glioma therapy. Full article
(This article belongs to the Special Issue Pharmacotherapy of Glioblastoma – Recent Improvements and Novel Perspectives)
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