Nanocomposite formulation for a sustained release of free drug and drug-loaded responsive nanoparticles: an approach for a local therapy of glioblastoma multiforme

Abstract

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.

Magnet-guided temozolomide and superparamagnetic iron oxide-loaded nanoparticles to enhance therapeutic efficacy in a glioma model

“…The results indicated that glioma tissue exhibited a higher accumulation of LTF than normal brain tissue, implying a potential targeting effect of LTF on the tumor cells. These ndings can be correlated with the immunohistochemistry data, demonstrating that an increased accumulation of LTF nanoparticles in glioma tissue could lead to a higher TMZ concentration, potentially causing a reduction in tumor cell proliferation and thus inhibiting glioma progression [20].…”

Magnet-Guided Temozolomide and Ferucarbotran Loaded Nanoparticles to Enhance Therapeutic Efficacy in Glioma Model

“…The findings indicated that glioma tissue exhibited a higher accumulation of LTF than normal brain tissue, implying a potential targeting effect of LTF on the tumor. We can relate the effect of a higher accumulation of LTF nanoparticles in glioma tissue with the immunohistochemistry data, which shows that more TMZ accumulation can cause reduced tumor cell proliferation and thus inhibit glioma progression [ 20 ].…”

Overcoming challenges in glioblastoma treatment: targeting infiltrating cancer cells and harnessing the tumor microenvironment

“…Additionally, the customization of different nanoparticles (Idlas et al, 2023) and the loading of various molecules (Lin et al, 2023) allow for unlimited potential therapeutic combinations. In some cases, nanoparticles loaded with chemotherapeutics are dispersed into gel matrices (Gu et al, 2022), which function as a shelter to reduce molecule degradation and unwanted cytotoxicity (Erthal et al, 2023). New formulations for in situ delivery aim at optimizing the effects of first-generation anti-glioblastoma agents such as carmustine and temozolomide, either alone or in combination, to maximize their curative effects, for example overcoming the resistance to TMZ using the O 6 alkylguanine DNA alkyltransferase inhibitor, dialdehyde O 6 benzylguanine (DABG), tested in xenograft (Chu et al, 2023) or intracranially delivered, minimizing peripheral toxicity (Chen et al, 2022;Iturrioz-Rodríguez et al, 2023).…”