Targeting transferrin receptor delivery of temozolomide for a potential glioma stem cell-mediated therapy

Sun, Ting; Wu, Haibin; Li, Yanyan; Huang, Yulun; Lin, Yu; Chen, Xiong-Hui; Han, Xing; Zhou, Youxin; Du, Ziwei

doi:10.18632/oncotarget.20165

Cited by 47 publications

(22 citation statements)

References 24 publications

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“…To address this research gap, we used pSiNP as a model NP due to its excellent biocompatibility and drug encapsulating capacity. Since TfR is overexpressed on GBM cells and on the luminal side of blood-brain barrier (BBB) 27,45 , it has become a popular target in a plethora of drug delivery studies. For example, Tf has been widely explored as a targeting ligand for improving BBB penetration of nanocarriers such as micelles 46 , liposomes 47 , and polymersomes 48 .…”

Section: Discussionmentioning

confidence: 99%

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Sheykhzadeh

Luo

Peng

et al. 2020

Sci Rep

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Mortality of glioblastoma multiforme (GBM) has not improved over the last two decades despite medical breakthroughs in the treatment of other types of cancers. Nanoparticles hold tremendous promise to overcome the pharmacokinetic challenges and off-target adverse effects. However, an inhibitory effect of nanoparticles by themselves on metastasis has not been explored. In this study, we developed transferrin-conjugated porous silicon nanoparticles (Tf@pSiNP) and studied their effect on inhibiting GBM migration by means of a microfluidic-based migration chip. This platform, designed to mimic the tight extracellular migration tracts in brain parenchyma, allowed high-content time-resolved imaging of cell migration. Tf@pSiNP were colloidally stable, biocompatible, and their uptake into GBM cells was enhanced by receptor-mediated internalisation. The migration of Tf@ pSiNP-exposed cells across the confined microchannels was suppressed, but unconfined migration was unaffected. The pSiNP-induced destabilisation of focal adhesions at the leading front may partially explain the migration inhibition. More corroborating evidence suggests that pSiNP uptake reduced the plasticity of GBM cells in reducing cell volume, an effect that proved crucial in facilitating migration across the tight confined tracts. We believe that the inhibitory effect of Tf@pSiNP on cell migration, together with the drug-delivery capability of pSiNP, could potentially offer a disruptive strategy to treat GBM.Glioblastoma multiforme (GBM) is the most prevalent and biologically aggressive type of primary brain tumour in adults 1 . Standard treatment is maximal surgical resection of a tumour followed by radiotherapy and temozolomide as an adjuvant chemotherapy 2 . Despite these advanced treatments, the survival rate of GBM patients is still less than 5% over five years, with a median overall survival of merely 15-23 months 3 . The factors that contribute to the high mortality are multifactorial. First and foremost, the diffuse invasion of GBM into brain parenchyma precludes complete surgical resection which leads to high recurrence 4 . Recurring GBM are usually multi-drug resistant, rendering chemotherapy ineffective 5 . On rare occasions, the high invasion and migration potential even leads to extracranial metastases 6 .The mechanisms of GBM invasion and migration are complex and encompasses the regulation of tumour microenvironment and of the molecular arrangement within the migrating GBM cells 7 . To enable migration across the small perivascular space, GBM cells have been shown to reduce their volume by releasing cytoplasmic fluid 8 . The reduction in cell size is particularly instrumental to GBM invasion into healthy brain tissue, since www.nature.com/scientificreports www.nature.com/scientificreports/ recombinant human Fibroblast Growth Factor basic (Gibco, PHG0024), and StemPro Neural Supplement (Gibco, A10508-01). The culture media also contained GlutaMAX (Gibco, 35050-061) and penicillin/streptomycin (Gibco, 15140-122). Cells were only used betwe...

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Section: Discussionmentioning

confidence: 99%

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Sheykhzadeh

Luo

Peng

et al. 2020

Sci Rep

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“…To increase the specificity for cancer targets, ligands attached to the surface of the nanocarriers were used for active targeting [50]. Such ligands are transferrin, antibodies, folic acid, enzymes, and macromolecules like proteins or carbohydrates [51][52][53][54][55]. In order to specifically target cancer cells, the nanoparticles surface may be optimized using different approaches, as it can be observed in the Figure 6.…”

Section: Modeling Bioavailability-a Real Challenge In Oncology Researchmentioning

confidence: 99%

Benefits of Nanomedicine for Therapeutic Intervention in Malignant Diseases

et al. 2019

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Cancer remains one of the most difficult to manage healthcare problems. The last two decades have been considered the golden age of cancer research, with major breakthroughs being announced on a regular basis. However, the major problem regarding cancer treatment is the incapability to selectively target cancer cells, with certain populations of tumors still remaining alive after treatment. The main focus of researchers is to develop treatments that are both effective and selective in targeting malignant cells. In this regard, bioavailability can be increased by overcoming the biological barriers encountered in the active agent’s pathway, creating carrier vehicles that have the ability to target malignant cells and effectively release the active agent. Since its appearance, nanomedicine has provided many answers to these challenges, but still, some expectations were not satisfied. In this review, we focused on the most recent developments in targeted drug delivery. Furthermore, a summary of different types of nanoparticles used to deliver active therapeutic agents in oncology is presented, along with details on the nanodrugs that were clinically approved by the Food and Drug Administration (FDA), until April 2019.

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“…Other receptors used to treat gliomas include vascular endothelial growth factor receptor (VEGFR) [ 210 ], platelet-derived growth factor receptor (PDGFR) [ 211 ], transforming growth factor receptor (TGFR) [ 212 ], fibroblast growth factor receptor (FGFR) [ 213 ], c-Met receptor [ 214 ], IL-4 receptor [ 215 ], urokinase-type plasminogen receptor (uPAR) [ 216 ], g-protein coupled receptors (GPCR) [ 217 ], transferrin [ 218 ], lactoferrin [ 219 ], low density lipoprotein receptor (LDL-R) and low density lipoprotein receptor-related protein (LRP1) [ 220 ], tenascin, folate receptor (FOLR) [ 221 ], and integrin-mediated targeting systems [ 222 ]. The VEGFR targeted antibody bevacizumab (Avastin) was FDA-approved to treat recurrent GBM [ 223 ], based on durable radiologic responses in a Phase II trial [ 224 ].…”

Section: Other Receptors/targeted Therapiesmentioning

confidence: 99%

Receptor-Targeted Glial Brain Tumor Therapies

Sharma

Debinski

2018

IJMS

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Among primary brain tumors, malignant gliomas are notably difficult to manage. The higher-grade tumors represent an unmet need in medicine. There have been extensive efforts to implement receptor-targeted therapeutic approaches directed against gliomas. These approaches include immunotherapies, such as vaccines, adoptive immunotherapy, and passive immunotherapy. Targeted cytotoxic radio energy and pro-drug activation have been designed specifically for brain tumors. The field of targeting through receptors progressed significantly with the discovery of an interleukin 13 receptor alpha 2 (IL-13RA2) as a tumor-associated receptor over-expressed in most patients with glioblastoma (GBM) but not in normal brain. IL-13RA2 has been exploited in novel experimental therapies with very encouraging clinical responses. Other receptors are specifically over-expressed in many patients with GBM, such as EphA2 and EphA3 receptors, among others. These findings are important in view of the heterogeneity of GBM tumors and multiple tumor compartments responsible for tumor progression and resistance to therapies. The combined targeting of multiple receptors in different tumor compartments should be a preferred way to design novel receptor-targeted therapeutic approaches in gliomas.

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Targeting transferrin receptor delivery of temozolomide for a potential glioma stem cell-mediated therapy

Cited by 47 publications

References 24 publications

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Transferrin-targeted porous silicon nanoparticles reduce glioblastoma cell migration across tight extracellular space

Benefits of Nanomedicine for Therapeutic Intervention in Malignant Diseases

Receptor-Targeted Glial Brain Tumor Therapies

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