Glioblastoma Stem Cells Drive Tumor Recurrence and Patient Relapse

Mann, Aneet; Ommeren, Randy Van; Manoranjan, Branavan; McFarlane, Nicole; Vora, Parvez; Venugopal, Chitra; Singh, Sheila K.

doi:10.1002/9781118356203.ch15

Cited by 3 publications

(3 citation statements)

References 83 publications

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“…Matrigel-based tube formation model was used to investigate the formation of vascularization in vitro as reported. 31,32 Thus, we observed tube formation in HUVECs treating with heparin, HD, DOX, and HD-DOX. The cytotoxicity of heparin on HUVECs was assessed first, and no detectable cytotoxic effect was found in vitro (data not shown).…”

Section: Effect Of Platelets Onmentioning

confidence: 81%

Antitumor and Antimetastasis Activities of Heparin-based Micelle Served As Both Carrier and Drug

Mei

Liu

Zhang

et al. 2016

ACS Appl. Mater. Interfaces

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Effective treatments for tumors are not easy to achieve due to the existence of metastases, which are responsible for most tumor death. Hence, a new drug delivery system is a pressing need, which should be biocompatible, stimuli-responsive, and multifunctional, including antitumor, antimetastasis, and antiangiogenesis effects. However, it is challenging to achieve all of these properties in one drug delivery system. Here, we developed a system of drug DOX and heparin into one self-assemble nanoparticle via pH-sensitive hydrazone bond and hydrophobic groups, deoxycholate. In the process, heparin itself was not only as the hydrophilic segments of the carrier, but also processed multiple biological functions such as antiangiogenesis and antimetastasis effect. The micelle nanoparticle HD-DOX processed good stability and acidic pH-triggered drug release property. After systemic administration, heparin-based micelle nanoparticle showed longer half-time and enhanced accumulation of DOX in tumors through the enhanced permeability and retention effect, leading to more efficient antitumor effects. In addition, heparin could hinder platelet-induced tumor cells epithelial-mesenchymal transition (EMT) and partially affect cell actin cytoskeletal arrangement, resulting in the disorganization of the actin cytoskeleton. Therefore, HD-DOX exhibited significant inhibitory effect on the metastasis in melanoma animal model in C57BL/6 mouse. Meanwhile, benefited from the antiangiogenesis effect of heparin, tube formations in endothelial cells were effectively inhibited and tumor vascular density was decreased by HD-DOX. Taken together, our study developed a self-assembly nanoplatform that both the drug and carrier had therapeutic effects with ideal antitumor efficacy.

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Section: Effect Of Platelets Onmentioning

confidence: 81%

Antitumor and Antimetastasis Activities of Heparin-based Micelle Served As Both Carrier and Drug

Mei

Liu

Zhang

et al. 2016

ACS Appl. Mater. Interfaces

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“…Cancer stem cells were usually correlated with drug resistance and relapse of malignant tumors 26 . Thus brain cancer stem cells were cultured and the cytotoxicity of liposomes on them was evaluated here.…”

Section: Resultsmentioning

confidence: 99%

“…Meanwhile, during the tumorigenesis of glioma, a few subpopulations of glioma cancer cells expressing CD133 are enriched to form cancer stem cells and exhibit greater tumorigenic potential than normal cancer cells 25 . BCSCs are commonly tolerated to chemotherapeutics and possess the capabilities of self-renewal and proliferation, which inevitably lead to the relapse of glioma 26 . Therefore, the synthesized anti-glioma effect with combined treatment of tumor cells, VM and BCSCs is important.…”

Section: Introductionmentioning

confidence: 99%

Dual Receptor Recognizing Cell Penetrating Peptide for Selective Targeting, Efficient Intratumoral Diffusion and Synthesized Anti-Glioma Therapy

Liu¹,

Mei²,

Xu³

et al. 2016

Theranostics

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Cell penetrating peptides (CPPs) were widely used for drug delivery to tumor. However, the nonselective in vivo penetration greatly limited the application of CPPs-mediated drug delivery systems. And the treatment of malignant tumors is usually followed by poor prognosis and relapse due to the existence of extravascular core regions of tumor. Thus it is important to endue selective targeting and stronger intratumoral diffusion abilities to CPPs. In this study, an RGD reverse sequence dGR was conjugated to a CPP octa-arginine to form a CendR (R/KXXR/K) motif contained tandem peptide R8-dGR (RRRRRRRRdGR) which could bind to both integrin αvβ3 and neuropilin-1 receptors. The dual receptor recognizing peptide R8-dGR displayed increased cellular uptake and efficient penetration ability into glioma spheroids in vitro. The following in vivo studies indicated the active targeting and intratumoral diffusion capabilities of R8-dGR modified liposomes. When paclitaxel was loaded in the liposomes, PTX-R8-dGR-Lip induced the strongest anti-proliferation effect on both tumor cells and cancer stem cells, and inhibited the formation of vasculogenic mimicry channels in vitro. Finally, the R8-dGR liposomal drug delivery system prolonged the medium survival time of intracranial C6 bearing mice by 2.1-fold compared to the untreated group, and achieved an exhaustive anti-glioma therapy including anti-tumor cells, anti-vasculogenic mimicry and anti-brain cancer stem cells. To sum up, all the results demonstrated that R8-dGR was an ideal dual receptor recognizing CPP with selective glioma targeting and efficient intratumoral diffusion, which could be further used to equip drug delivery system for effective glioma therapy.

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