Nanoparticle‐Programmed Self‐Destructive Neural Stem Cells for Glioblastoma Targeting and Therapy

Cheng, Yu; Morshed, Ramin A.; Cheng, Shih Hsun; Tobias, Alex L.; Auffinger, Brenda; Wainwright, Derek A.; Zhang, Lingjiao; Yunis, Catherine; Han, Yu; Chen, Chin Tu; Lo, Leu‐Wei; Aboody, Karen S.; Ahmed, Atique U.; Lesniak, Maciej S.

doi:10.1002/smll.201301111

Cited by 81 publications

(86 citation statements)

References 29 publications

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“…MIAMI cell-mediated delivery may also result in better Fc-diOH retention within the tumor environment, constituting another advantage of this cell delivery system over LNCs alone. Consistent with our results, Cheng et al 38 recently reported that intratumoral and contralateral injections of a neural stem cell line loaded with doxorubicin (Dox)-mesoporous silica nanoparticles elicited a significantly stronger therapeutic effect than Doxmesoporous silica nanoparticles alone in the U87MG GB model. Dox was found to be widely distributed specifically within the tumor following the use of this neural stem cell line carrier.…”

Section: Discussionsupporting

confidence: 93%

Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules

Clavreul¹,

Montagu²,

Lainé³

et al. 2015

IJN

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Recently developed drug delivery nanosystems, such as lipid nanocapsules (LNCs), hold great promise for the treatment of glioblastomas (GBs). In this study, we used a subpopulation of human mesenchymal stem cells, "marrow-isolated adult multilineage inducible" (MIAMI) cells, which have endogenous tumor-homing activity, to deliver LNCs containing an organometallic complex (ferrociphenol or Fc-diOH), in the orthotopic U87MG GB model. We determined the optimal dose of Fc-diOH-LNCs that can be carried by MIAMI cells and compared the efficacy of Fc-diOH-LNC-loaded MIAMI cells with that of the free-standing Fc-diOH-LNC system. We showed that MIAMI cells entrapped an optimal dose of about 20 pg Fc-diOH per cell, with no effect on cell viability or migration capacity. The survival of U87MG-bearing mice was longer after the intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells than after the injection of Fc-diOH-LNCs alone. The greater effect of the Fc-diOH-LNC-loaded MIAMI cells may be accounted for by their peritumoral distribution and a longer residence time of the drug within the tumor. These results confirm the potential of combinations of stem cell therapy and nanotechnology to improve the local tissue distribution of anticancer drugs in GB.

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Section: Discussionsupporting

confidence: 93%

Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules

Clavreul¹,

Montagu²,

Lainé³

et al. 2015

IJN

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International audience

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“…For this approach, a nano-scaled drug delivery system (e.g. functionalized nanoparticles [41]) allowing for [I-125]ITdU to be efficiently transported across the BBB for targeting of GSC could be a solution.…”

Section: Discussionmentioning

confidence: 99%

Hedgehog signaling sensitizes Glioma stem cells to endogenous nano-irradiation

et al. 2014

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The existence of therapy resistant glioma stem cells is responsible for the high recurrence rate and incurability of glioblastomas. The Hedgehog pathway activity plays an essential role for self-renewal capacity and survival of glioma stem cells. We examined the potential of the Sonic hedgehog ligand for sensitizing of glioma stem cells to endogenous nano-irradiation. We demonstrate that the Sonic hedgehog ligand preferentially and efficiently activats glioma stem cells to enter the radiation sensitive G2/M phase. Concomitant inhibition of de novo thymidine synthesis with fluorodeoxyuridine and treatment with the Auger electron emitting thymidine analogue 5-[I-125]-Iodo-4′-thio-2′-deoxyuridine ([I-125]ITdU) leads to a fatal nano-irradiation in sensitized glioma stem cells. Targeting of proliferating glioma stem cells with DNA-incorporated [I-125]ITdU efficiently invokes the intrinsic apoptotic pathway despite active DNA repair mechanisms. Further, [I-125]ITdU completely inhibits survival of glioma stem cells in vitro. Analysis of non-stem glioblastoma cells and normal human astrocytes reveals that glioma stem cells differentially respond to Sonic hedgehog ligand. These data demonstrate a highly efficient and controllable single-cell kill therapeutic model for targeting glioma stem cells.

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“…155 Nanoparticles have also been used for cell tracking. NSC loaded with iron oxide nanoparticles can be transplanted and subsequently tracked using noninvasive magnetic resonance imaging.…”

Section: Advances In Polymer Chemistry and Nanoparticle Delivery For mentioning

confidence: 99%

Enabling nanomaterial, nanofabrication and cellular technologies for nanoneuromedicines

Mallapragada

Brenza

McMillan

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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Nanoparticulate delivery systems represent an area of particular promise for nanoneuromedicines. They possess significant potential for desperately needed therapies designed to combat a range of disorders associated with aging. As such, the field was selected as the focus for the 2014 meeting of the American Society for Nanomedicine. Regenerative, protective, immune modulatory, anti-microbial and anti-inflammatory products, or imaging agents are readily encapsulated in or conjugated to nanoparticles and as such facilitate the delivery of drug payloads to specific action sites across the blood-brain barrier. Diagnostic imaging serves to precisely monitor disease onset and progression while neural stem cell replacement can regenerate damaged tissue through control of stem cell fates. These, taken together, can improve disease burden and limit systemic toxicities. Such enabling technologies serve to protect the nervous system against a broad range of degenerative, traumatic, metabolic, infectious and immune disorders.

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Nanoparticle‐Programmed Self‐Destructive Neural Stem Cells for Glioblastoma Targeting and Therapy

Cited by 81 publications

References 29 publications

Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules

Targeting and treatment of glioblastomas with human mesenchymal stem cells carrying ferrociphenol lipid nanocapsules

Hedgehog signaling sensitizes Glioma stem cells to endogenous nano-irradiation

Enabling nanomaterial, nanofabrication and cellular technologies for nanoneuromedicines

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