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Pharmaceutics
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Nano-Based Technology for Glioblastoma
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Nano-Based Technology for Glioblastoma

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

Deadline for manuscript submissions: 20 April 2026 | Viewed by 4800

Special Issue Editors

Dr. Maria João Ramalho

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Guest Editor
1. LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
2. ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
Interests: drug delivery; targeted therapy; brain delivery; brain cancer; glioblastoma; cancer therapy; neurodegenerative disease therapy; biophysical models; drug–membrane interactions
Special Issues, Collections and Topics in MDPI journals
Dr. Joana Peixoto

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Guest Editor
1. i3S - i3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal
2. LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
Interests: brain cancer; gliomagenesis; organoids; targeted therapy

Special Issue Information

Dear Colleagues,

Nano-based technology offers promising avenues for treating glioblastoma, the most common and deadliest form of primary brain cancer in adults. Innovative approaches utilizing nanoparticles to deliver therapeutic agents directly to tumor cells have been successfully designed to enhance drug efficacy while minimizing off-target effects. Nanoparticles can not only penetrate the blood–brain barrier, allowing for targeted drug delivery to tumor cells, but can also be engineered to release drugs in response to specific stimuli within the tumor microenvironment. The goal of these platforms is to reduce systemic toxicity, while also enabling combination therapies, by delivering multiple drugs simultaneously to avoid drug resistance and improve treatment efficacy. Overall, nano-based technology holds immense potential for revolutionizing glioblastoma therapy, offering hope for improved patient outcomes and survival rates.

Under this scope, we are pleased to invite you to participate in the Special Issue of Pharmaceutics, entitled “Nano-Based Technology for Glioblastoma Therapy.” This Special Issue aims to include original research articles and reviews within, but not limited to, the following research areas: design and development of nanoparticles that specifically target glioblastoma cells; strategies to enhance the ability of nanoparticles to penetrate the blood–brain barrier; engineering stimuli-responsive nanoparticles or immunomodulatory nanoparticles; nano-delivery platforms for combination therapies; imaging, diagnosis, and theranostics with nano-based systems, among others.

We look forward to receiving your contributions.

Dr. Maria João Ramalho
Dr. Joana Peixoto
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

  • nanoparticles
  • glioblastoma
  • blood–brain barrier
  • diagnosis
  • therapy
  • drug delivery
  • nose-to-brain delivery
  • targeted delivery
  • surface modification

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Published Papers (4 papers)

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Research

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27 pages, 2468 KB  
Article
Targeted Fluoxetine Delivery Using Folic Acid-Modified PLGA Nanoparticles for Selective Uptake by Glioblastoma Cells
by Maria João Ramalho, Carina Nóbrega, Stéphanie Andrade, Jorge Lima, Joana Angélica Loureiro and Maria Carmo Pereira
Pharmaceutics 2025, 17(9), 1116; https://doi.org/10.3390/pharmaceutics17091116 - 27 Aug 2025
Viewed by 399
Abstract
Background/Objectives: The conventional treatment of glioblastoma (GBM) with alkylating agents is not curative. The protein O6-methylguanine DNA methyltransferase (MGMT) is a significant limitation, being able to repair drug-induced DNA damage. Thus, exploring non-alkylating agents already approved by the FDA is imperative. The [...] Read more.
Background/Objectives: The conventional treatment of glioblastoma (GBM) with alkylating agents is not curative. The protein O6-methylguanine DNA methyltransferase (MGMT) is a significant limitation, being able to repair drug-induced DNA damage. Thus, exploring non-alkylating agents already approved by the FDA is imperative. The antidepressant fluoxetine (FL) has been explored due to its anti-cancer properties. However, its first-pass effect and its non-targeted distribution to brain tissue are major limitations of FL’s administration, which is conventionally orally administered. Thus, the primary objective of this work was the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) tailored with folic acid (FA) for FL delivery to GBM cells. Methods: A Central Composite Design (CCD) was applied to optimize the NPs. Results: The developed FA-functionalized PLGA NPs exhibited physicochemical properties suitable for brain-targeted delivery. The final formulation presented an average diameter of 167 ± 8 nm, a polydispersity index (PdI) of 0.23 ± 0.07, and a zeta potential of −22.2 ± 0.3 mV. The encapsulation efficiency (EE) and loading capacity (LC) values were 44.4 ± 3.8% and 3.1 ± 0.3%, respectively. In vitro studies demonstrated that the NPs are stable in storage and simulated physiological conditions and can maintain a controlled and slow-release profile of FL for 17 days. In vitro cell uptake experiments demonstrated that conjugation with FA enhances the NPs’ internalization in GBM cells overexpressing folate receptors through endocytosis mediated by this receptor. Furthermore, in vitro cytotoxicity experiments demonstrated that the FL encapsulation in the developed NPs maintains drug efficacy, as well as it was able to increase cell sensitivity to treatment with an alkylating agent. Conclusions: These results suggest that the developed NPs are effective nanocarriers, either as a standalone therapy or as a chemosensitizer in combination with the standard GBM treatment. Full article
(This article belongs to the Special Issue Nano-Based Technology for Glioblastoma)
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21 pages, 3205 KB  
Article
Click on Click: Click-Flavone Glycosides Encapsulated in Click-Functionalised Polymersomes for Glioblastoma Therapy
by Nuno M. Saraiva, Ana Alves, Ana Isabel Barbosa, Andreia Marinho, Salette Reis, Marta Correia-da-Silva and Paulo C. Costa
Pharmaceutics 2025, 17(6), 771; https://doi.org/10.3390/pharmaceutics17060771 - 12 Jun 2025
Viewed by 736
Abstract
In this study, three new 3,7-dihydroxyflavone (1) derivatives with different sugars were designed and synthesised by click chemistry. Click chemistry requires the previously modification of building blocks with azide and alkyne groups and therefore, the 3,7-dihydroxyflavone (1) was first [...] Read more.
In this study, three new 3,7-dihydroxyflavone (1) derivatives with different sugars were designed and synthesised by click chemistry. Click chemistry requires the previously modification of building blocks with azide and alkyne groups and therefore, the 3,7-dihydroxyflavone (1) was first converted in 3,7-(prop-2-yn-yloxy)flavone (2) and acetobromo-α-D-glucose (3) was converted into 2,3,4,6-tetra-O-acetyl-β-glucopyranosyl azide (4). Subsequently, a click reaction was performed via copper-catalysed cycloaddition (CuAAC) between 2 and 4, as well as between 2 and 2-acetamido-3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranosyl (AG931) and, 2 and commercial 2-azidoethyl 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl (AG358), resulting in three distinct disubstituted flavone glycosides (5a–5c). Biological assays performed on L929 fibroblast cell lines and human glioblastoma astrocytoma U-251 cell lines indicated cytocompatibility with fibroblasts and reduced metabolic activity of GBM cells in the presence of compound 5b and 5c. To enhance therapeutic effect, improve local drug delivery, and overcome solubility issues of these high molecular weight compounds, the synthesised compounds were encapsulated in polymeric particles (polymersomes, PMs) composed of polylactic acid-polyethylene glycol (PEG-PLA) functionalized, once more by click chemistry, with 0.1 mol% transferrin mimetic (T7—HRPYIAH) peptide. The PMs were prepared by solvent displacement and exhibited stability over 100 days, encapsulation efficiency of 39–93%, and mean size diameters of 120–180 nm. The toxicity assays of the PMs on the U-251 cell line showed a significant decrease in metabolic activity, supporting the potential of this delivery system against GBM. Among the PMs tested, the flavone 5c-based PM demonstrated the highest efficacy. Full article
(This article belongs to the Special Issue Nano-Based Technology for Glioblastoma)
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Review

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25 pages, 814 KB  
Review
Nanoparticles for Glioblastoma Treatment
by Dorota Bartusik-Aebisher, Kacper Rogóż and David Aebisher
Pharmaceutics 2025, 17(6), 688; https://doi.org/10.3390/pharmaceutics17060688 - 23 May 2025
Cited by 1 | Viewed by 1056
Abstract
GBM is the most common and aggressive primary brain tumor in adults, characterized by low survival rates, high recurrence, and resistance to conventional therapies. Traditional diagnostic and therapeutic methods remain limited due to the difficulty in permeating the blood–brain barrier (BBB), diffuse tumor [...] Read more.
GBM is the most common and aggressive primary brain tumor in adults, characterized by low survival rates, high recurrence, and resistance to conventional therapies. Traditional diagnostic and therapeutic methods remain limited due to the difficulty in permeating the blood–brain barrier (BBB), diffuse tumor cell infiltration, and tumor heterogeneity. In recent years, nano-based technologies have emerged as innovative approaches for the detection and treatment of GBM. A wide variety of nanocarriers, including dendrimers, liposomes, metallic nanoparticles, carbon nanotubes, carbon dots, extracellular vesicles, and many more demonstrate the ability to cross the BBB, precisely deliver therapeutic agents, and enhance the effects of radiotherapy and immunotherapy. Surface functionalization, peptide modification, and cell membrane coating improve the targeting capabilities of nanostructures toward GBM cells and enable the exploitation of their photothermal, magnetic, and optical properties. Furthermore, the development of miRNA nanosponge systems offers the simultaneous inhibition of multiple tumor growth mechanisms and the modulation of the immunosuppressive tumor microenvironment. This article presents current advancements in nanotechnology for GBM, with a particular focus on the characteristics and advantages of specific groups of nanoparticles, including their role in radiosensitization. Full article
(This article belongs to the Special Issue Nano-Based Technology for Glioblastoma)
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33 pages, 2790 KB  
Review
Emerging Approaches in Glioblastoma Treatment: Modulating the Extracellular Matrix Through Nanotechnology
by Miguel Horta, Paula Soares, Catarina Leite Pereira and Raquel T. Lima
Pharmaceutics 2025, 17(2), 142; https://doi.org/10.3390/pharmaceutics17020142 - 21 Jan 2025
Cited by 4 | Viewed by 1824
Abstract
Glioblastoma’s (GB) complex tumor microenvironment (TME) promotes its progression and resistance to therapy. A critical component of TME is the extracellular matrix (ECM), which plays a pivotal role in promoting the tumor’s invasive behavior and aggressiveness. Nanotechnology holds significant promise for GB treatment, [...] Read more.
Glioblastoma’s (GB) complex tumor microenvironment (TME) promotes its progression and resistance to therapy. A critical component of TME is the extracellular matrix (ECM), which plays a pivotal role in promoting the tumor’s invasive behavior and aggressiveness. Nanotechnology holds significant promise for GB treatment, with the potential to address challenges posed by both the blood-brain barrier and the GB ECM. By enabling targeted delivery of therapeutic and diagnostic agents, nanotechnology offers the prospect of improving treatment efficacy and diagnostic accuracy at the tumor site. This review provides a comprehensive exploration of GB, including its epidemiology, classification, and current treatment strategies, alongside the intricacies of its TME. It highlights nanotechnology-based strategies, focusing on nanoparticle formulations such as liposomes, polymeric nanoparticles, and gold nanoparticles, which have shown promise in GB therapy. Furthermore, it explores how different emerging nanotechnology strategies modulate the ECM to overcome the challenges posed by its high density, which restricts drug distribution within GB tumors. By emphasizing the intersection of nanotechnology and GB ECM, this review underscores an innovative approach to advancing GB treatment. It addresses the limitations of current therapies, identifies new research avenues, and emphasizes the potential of nanotechnology to improve patient outcomes. Full article
(This article belongs to the Special Issue Nano-Based Technology for Glioblastoma)
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