Polymeric Nanoparticles for the Treatment of Malignant Gliomas

Mahmoud, Basant Salah; Alamri, Ali H.; McConville, Christopher

doi:10.3390/cancers12010175

Cited by 70 publications

(53 citation statements)

References 216 publications

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“…With this strategy in mind, we have developed and characterized a CXCL12 delivery system based on Alg/Chit NPs. NPs made of polyelectrolyte complexes such as Alg/Chit are particularly adapted for addressing molecules to the brain tissue and have potential to treat gliomas [42,43]. They can easily be freeze-dried and reconstituted without affecting the size, release capacity, and bioactivity of the solute contained within [31].…”

Section: Discussionmentioning

confidence: 99%

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

et al. 2020

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Chitosan (Chit) currently used to prepare nanoparticles (NPs) for brain application can be complexed with negatively charged polymers such as alginate (Alg) to better entrap positively charged molecules such as CXCL12. A sustained CXCL12 gradient created by a delivery system can be used, as a therapeutic approach, to control the migration of cancerous cells infiltrated in peri-tumoral tissues similar to those of glioblastoma multiforme (GBM). For this purpose, we prepared Alg/Chit NPs entrapping CXCL12 and characterized them. We demonstrated that Alg/Chit NPs, with an average size of ~250 nm, entrapped CXCL12 with ~98% efficiency for initial mass loadings varying from 0.372 to 1.490 µg/mg NPs. The release kinetic profiles of CXCL12 were dependent on the initial mass loading, and the released chemokine from NPs after seven days reached 12.6%, 32.3%, and 59.9% of cumulative release for initial contents of 0.372, 0.744, and 1.490 µg CXCL12/mg NPs, respectively. Mathematical modeling of released kinetics showed a predominant diffusive process with strong interactions between Alg and CXCL12. The CXCL12-NPs were not toxic and did not promote F98 GBM cell proliferation, while the released CXCL12 kept its chemotaxis effect. Thus, we developed an efficient and tunable CXCL12 delivery system as a promising therapeutic strategy that aims to be injected into a hydrogel used to fill the cavity after surgical tumor resection. This system will be used to attract infiltrated GBM cells prior to their elimination by conventional treatment without affecting a large zone of healthy brain tissue.

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Section: Discussionmentioning

confidence: 99%

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

et al. 2020

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“…In this context, revealing the feasible molecular mechanisms contributing to the formation and progression of this tumor might be a pivotal step in the generation of new and more effective precision therapies [18][19][20][21]. In this study, we explored RPS27L overexpression in gliomas and demonstrated that RPS27L expression increased as an increase in tumor grade and that RPS27L was associated with the overall survival of patients, which suggested that RPS27L played an important role in glioma malignancy.…”

Section: Discussionmentioning

confidence: 92%

WITHDRAWN: Ribosomal Protein S27-Like is overexpressed in glioma cells and inhibition of RPS27L expression suspends the tumorigenesis

Sun

Xue

Yan

et al. 2020

Preprint

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Background: Ribosomal Protein S27-Like is an evolutionarily conserved ribosomal protein and the role of RPS27L influencing the malignance of several cancers has been reported. However, its effects on glioma were still unknown. This investigation aims to characterize the clinical significance and the biological functions of RPS27L in gliomas.Methods: TCGA databases were explored to analyze the correlation between RPS27L expression and the clinical characteristics of glioma patients. Immunohistochemical staining was performed on glioma cases and normal brain tissues. The function of RPS27L in glioma was further explored using U87MG and A172 cell lines and a orthotopic xenograft model of nude mice.Results: Data obtained from TCGA database showed higher expression of RPS27L in glioma than normal, and the overall survival was lower in the high expression group. Immunohistochemistry showed the expression levels of RPS27L were increased with the tumor grade rising in gliomas. Functional assays showed knockdown of RPS27L inhibited proliferation, cell cycle transition, migration and invasion, while promoted apoptosis. Data of western blot indicated that knockdown of RPS27L increased the level of p21，Bax and Cleaved Caspase-3 while decreased the level of CDK4, cyclinD1, cyclinE1, Bcl-2 and MMP2, MMP9 in glioma cells. In vivo, the growth of orthotopic glioma xenografts was suppressed by expression of RPS27L shRNA, and the tumors with RPS27L shRNA showed less aggressiveness and reduced expression of Ki67, Bcl-2 and MMP2. Conclusions: RPS27L is overexpressed in glioma cells. Knockdown of RPS27L could inhibit the proliferation, migration and invasion while promote apoptosis of glioma cells in vitro and in vivo. RPS27L might be a potential prognostic biomarker and possible target for future therapy in glioma.

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“…These polymeric nanoparticles are used as carriers for different drugs such as in chemotherapy, which are either adsorbed on the surface or encapsulated within the nanoparticles. These improve the release kinetics, the compatibility with some active agents, have no oxidation issues (as with phospholipids), and enhance shelf-life [ 82 ]. Other studies [ 63 , 68 ] also detected VEGF in antiangiogenic therapy but did not quantify the protein expression after therapy.…”

Section: Discussionmentioning

confidence: 99%

Antiangiogenic Targets for Glioblastoma Therapy from a Pre-Clinical Approach, Using Nanoformulations

Rego

Alves

Nucci

et al. 2020

IJMS

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Glioblastoma (GBM) is the most aggressive tumor type whose resistance to conventional treatment is mediated, in part, by the angiogenic process. New treatments involving the application of nanoformulations composed of encapsulated drugs coupled to peptide motifs that direct drugs to specific targets triggered in angiogenesis have been developed to reach and modulate different phases of this process. We performed a systematic review with the search criterion (Glioblastoma OR Glioma) AND (Therapy OR Therapeutic) AND (Nanoparticle) AND (Antiangiogenic OR Angiogenesis OR Anti-angiogenic) in Pubmed, Scopus, and Cochrane databases, in which 312 articles were identified; of these, only 27 articles were included after selection and analysis of eligibility according to the inclusion and exclusion criteria. The data of the articles were analyzed in five contexts: the characteristics of the tumor cells; the animal models used to induce GBM for antiangiogenic treatment; the composition of nanoformulations and their physical and chemical characteristics; the therapeutic anti-angiogenic process; and methods for assessing the effects on antiangiogenic markers caused by therapies. The articles included in the review were heterogeneous and varied in practically all aspects related to nanoformulations and models. However, there was slight variance in the antiangiogenic effect analysis. CD31 was extensively used as a marker, which does not provide a view of the effects on the most diverse aspects involved in angiogenesis. Therefore, the present review highlighted the need for standardization between the different approaches of antiangiogenic therapy for the GBM model that allows a more effective meta-analysis and that helps in future translational studies.

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Polymeric Nanoparticles for the Treatment of Malignant Gliomas

Cited by 70 publications

References 216 publications

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

WITHDRAWN: Ribosomal Protein S27-Like is overexpressed in glioma cells and inhibition of RPS27L expression suspends the tumorigenesis

Antiangiogenic Targets for Glioblastoma Therapy from a Pre-Clinical Approach, Using Nanoformulations

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