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Glioblastoma multiforme (GBM) is a highly aggressive brain cancer associated with poor survival rates. We developed novel mesoporous silica nanoparticles (MSNs)-based nanocarriers for pH-responsive delivery of a therapeutic drug Paclitaxel (PTX) to GBM tumor cells. The pores of MSNs are loaded with PTX, which is retained by β-cyclodextrin (CD) moieties covalently linked to the pore entrances through a hydrazone linkage, which is cleavable in weakly acidic environment. Furthermore, we utilized a host-guest interaction between the adamantane and capping CD moieties to further functionalize the surface with a potential glioma-targeting oligopeptide chlorotoxin (CHX). In vitro studies in the U87 GBM cell line show decreased uptake, but increased toxicity of CHX-modified nanoparticles compared to CHX-free nanoparticles. The obtained results are promising toward development of advanced drug nanocarriers, which may target the overexpressed receptors in cancer tissues and utilize their weakly acidic environment for triggering the drug release, potentially leading to more efficient cancer treatments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Malignant gliomas are a type of primary brain tumour that originates in glial cells. Among them, glioblastoma multiforme (GBM) is the most common and the most aggressive brain tumour in adults, classified as grade IV by the World Health Organization. The standard care for GBM, known as the Stupp protocol includes surgical resection followed by oral chemotherapy with temozolomide (TMZ). This treatment option provides a median survival prognosis of only 16-18 months to patients mainly due to tumour recurrence. Therefore, enhanced treatment options are urgently needed for this disease. Here we show the development, characterization, and in vitro and in vivo evaluation of a new composite material for local therapy of GBM post-surgery. We developed responsive nanoparticles that were loaded with paclitaxel (PTX), and that showed penetration in 3D spheroids and cell internalization. These nanoparticles were found to be cytotoxic in 2D (U-87 cells) and 3D (U-87 spheroids) models of GBM. The incorporation of these nanoparticles into a hydrogel facilitates their sustained release in time. Moreover, the formulation of this hydrogel containing PTX-loaded responsive nanoparticles and free TMZ was able to delay tumour recurrence in vivo after resection surgery. Therefore, our formulation represents a promising approach to develop combined local therapies against GBM using injectable hydrogels containing nanoparticles., (© 2023. The Author(s).)

Nanomedicine is currently focused on the design and development of nanocarriers that enhance drug delivery to the brain to address unmet clinical needs for treating neuropsychiatric disorders and neurological diseases. Polymer and lipid-based drug carriers are advantageous for delivery to the central nervous system (CNS) due to their safety profiles, drug-loading capacity, and controlled-release properties. Polymer and lipid-based nanoparticles (NPs) are reported to penetrate the blood-brain barrier (BBB) and have been extensively assessed in in vitro and animal models of glioblastoma, epilepsy, and neurodegenerative disease. Since approval by the Food and Drug Administration (FDA) of intranasal esketamine for treatment of major depressive disorder, intranasal administration has emerged as an attractive route to bypass the BBB for drug delivery to the CNS. NPs can be specifically designed for intranasal administration by tailoring their size and coating with mucoadhesive agents or other moieties that promote transport across the nasal mucosa. In this review, unique characteristics of polymeric and lipid-based nanocarriers desirable for drug delivery to the brain are explored in addition to their potential for drug repurposing for the treatment of CNS disorders. Progress in intranasal drug delivery using polymeric and lipid-based nanostructures for the development of treatments of various neurological diseases are also described.

The treatment for glioblastoma multiforme (GBM) has not changed for more than 20 years while the prognosis for the patients is still poor and most of them survive less than 1 year after diagnosis. The standard of care for GBM is comprised of surgical resection followed by radiotherapy and oral chemotherapy with temozolomide. The placement of carmustine wafers in the brain after tumour removal is added in cases of recurrent glioma. Significant research is underway to improve the GBM therapy outcome and patient quality of life. Biomaterials are in the front line of the research focus for new treatment options. Specially, biocompatible polymers have been proposed in hydrogel-based formulations aiming at injectable and localized therapies. These formulations can comprise many different pharmacological agents such as chemotherapeutic drugs, nanoparticles, cells, nucleic acids, and diagnostic agents. In this manuscript, we review the most recent formulations developed and tested both in vitro and in vivo using different types of hydrogels. Firstly, we describe three common types of thermo-responsive polymers addressing the advantages and drawbacks of their formulations. Then, we focus on formulations specifically developed for GBM treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Cancer nanomedicines have shown promise in combination immunotherapy, thus far mostly preclinically but also already in clinical trials. Combining nanomedicines with immunotherapy aims to reinforce the cancer-immunity cycle, via potentiating key steps in the immune reaction cascade, namely antigen release, antigen processing, antigen presentation, and immune cell-mediated killing. Combination nano-immunotherapy can be realized via three targeting strategies, i.e., by targeting cancer cells, targeting the tumor immune microenvironment, and targeting the peripheral immune system. The clinical potential of nano-immunotherapy has recently been demonstrated in a phase III trial in which nano-albumin paclitaxel (Abraxane®) was combined with atezolizumab (Tecentriq®) for the treatment of patients suffering from advanced triple-negative breast cancer. In the present paper, besides strategies and initial (pre)clinical success stories, we also discuss several key challenges in nano-immunotherapy. Taken together, nanomedicines combined with immunotherapy are gaining significant attention, and it is anticipated that they will play an increasingly important role in clinical cancer therapy.

Aim: Cell repopulation of tissue-engineered vascular grafts (TEVGs) from decellularized arterial scaffolds is limited by dense concentric tunica media layers which impede cells migrating radially between the layers. We aimed to develop and validate a new microneedle device to modify decellularized carotid arteries with radial microchannels to enhance medial layer repopulation. Material & methods: Modified decellularized porcine arteries were seeded with rat mesenchymal stem cells using either standard longitudinal injection, or a dual vacuum-perfusion bioreactor. Mechanical tests were used to assess the arterial integrity following modification. Results & conclusion: The method herein achieved radial recellularization of arteries in vitro without significant loss of mechanical integrity, Thus, we report a novel method for successful radial repopulation of decellularized carotid artery-based tissue-engineered vascular grafts.