TRAIL conjugated to nanoparticles exhibits increased anti-tumor activities in glioma cells and glioma stem cells in vitro and in vivo

Perlstein, Benny; Finniss, Susan; Miller, Claudia; Okhrimenko, Hana; Kazimirsky, Gila; Cazacu, Simona; Lee, Hae Kyung; Lemke, Nancy; Brodie, Shlomit; Umansky, Félix; Rempel, Sandra A.; Rosenblum, Mark L.; Mikklesen, Tom; Margel, Shlomo; Brodie, Chaya

doi:10.1093/neuonc/nos248

Cited by 63 publications

(59 citation statements)

References 45 publications

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“…Additionally, NPs loaded with siRNAs targeting specific CSC genes [129][130][131] or with CSC inhibitory molecules [132][133][134][135][136] have been generated. To improve the specific targeting of CSCs, it might be worthwhile to create NPs loaded with both phytocompounds and non-phytochemical payloads.…”

Section: Discussionmentioning

confidence: 99%

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

et al. 2015

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Glioblastoma multiforme (GBM) are extremely lethal and still poorly treated primary brain tumors, characterized by the presence of highly tumorigenic cancer stem cell (CSC) subpopulations, considered responsible for tumor relapse. In order to successfully eradicate GBM growth and recurrence, new anti-cancer strategies selectively targeting CSCs should be designed. CSCs might be eradicated by targeting some of their cell surface markers and transporters, inducing their differentiation, impacting their hyper-glycolytic metabolism, inhibiting CSC-related signaling pathways and/or by targeting their microenvironmental niche. In this regard, phytocompounds such as curcumin, isothiocyanates, resveratrol and epigallocatechin-3-gallate have been shown to prevent or reverse cancer-related epigenetic dysfunctions, reducing tumorigenesis, preventing metastasis and/or increasing chemotherapy and radiotherapy efficacy. However, the actual bioavailability and metabolic processing of phytocompounds is generally unknown, and the presence of the blood brain barrier often represents a limitation to glioma treatments. Nowadays, nanoparticles (NPs) can be loaded with therapeutic compounds such as phytochemicals, improving their bioavailability and their targeted delivery within the GBM tumor bulk. Moreover, NPs can be designed to increase their tropism and specificity toward CSCs by conjugating their surface with antibodies specific for CSC antigens, with ligands or with glucose analogues. Here we discuss the use of phytochemicals as anti-glioma agents and the applicability of phytochemical-loaded NPs as drug delivery systems to target GBM. Additionally, we provide some examples on how NPs can be specifically formulated to improve CSC targeting.

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Section: Discussionmentioning

confidence: 99%

Targeting Glioblastoma with the Use of Phytocompounds and Nanoparticles

et al. 2015

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“…There are several studies using variations of nanovector or nanoparticle encapsulation of TRAIL (25)(26)(27). The most recent study (25), evaluated the ability of nanoparticle-conjugated TRAIL (NP-TRAIL) to induce apoptosis of glioma cells in vitro and in vivo. When directly compared with TRAIL in vitro, the NP-TRAIL offered only modest improvement in apoptotic induction.…”

Section: Discussionmentioning

confidence: 99%

“…When directly compared with TRAIL in vitro, the NP-TRAIL offered only modest improvement in apoptotic induction. The in vivo survival curve was significantly better for NP-TRAIL, but it should be noted that the NP-TRAIL or TRAIL were administered directly to the tumor site in the brain of the rats, and it is unclear whether the improvement in treatment efficacy would be maintained with systemic treatment (25). The remaining studies were performed in a single laboratory group using variations on TRAIL conjugated to nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin Fc Domain Fusion to TRAIL Significantly Prolongs Its Plasma Half-Life and Enhances Its Antitumor Activity

Wang

Davis

2014

Molecular Cancer Therapeutics

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TRAIL (Apo2L) is a potent inducer of cell death. Interest in TRAIL has increased, following the observation that TRAIL can selectively kill a wide variety of human cancer cells without killing normal cells both in vitro and when grown as xenografts. Therefore, TRAIL has been proposed as a promising anticancer agent and currently is being tested in clinical trials. However, recombinant TRAIL has a very short plasma half-life, which limits its therapeutic potential. To overcome this limitation, we investigated the ability of the human IgG1 fragment crystallizable region (Fc) to enhance TRAIL stability. In this report, we show that Fc-TRAIL chimeric protein displays higher specific activity in vitro and a significantly longer half-life in mice than recombinant human TRAIL (rh-TRAIL). No short-term toxicity, especially liver toxicity, was observed. More importantly, Fc-TRAIL was much more effective in inhibiting tumor growth in a xenograft tumor model compared with rh-TRAIL. Our data suggest that fusion of Fc to TRAIL is able to improve the bioavailability and activity of TRAIL both in vitro and in vivo, and Fc-TRAIL may be explored for future clinical applications in cancer treatment and prevention. Mol Cancer Ther; 13(3); 643-50. Ó2014 AACR.

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“…Nanoparticles are designed to override the absence of cancer cell-specific targeting ability of conventional chemotherapy. 41 Recently, TRAIL was conjugated with magnetic ferric oxide nanoparticles and showed increased apoptotic activity against different human glioma cells and glioma stem cells, as compared with free recombinant TRAIL. When the effects of TRAIL and nanoparticles-conjugated TRAIL were compared on animal survival using U251 xenografts, the results showed that the latter significantly prolonged survival.…”

Section: Trail Administrationmentioning

confidence: 99%