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Nanoparticle-programmed self-destructive neural stem cells for glioblastoma targeting and therapy.

ABSTRACT: A 3-step glioblastoma-tropic delivery and therapy method using nanoparticle programmed self-destructive neural stem cells (NSCs) is demonstrated in vivo: 1) FDA-approved NSCs for clinical trials are loaded with pH-sensitive MSN-Dox; 2) the nanoparticle conjugates provide a delayed drug-releasing mechanism and allow for NSC migration towards a distant tumor site; 3) NSCs eventually undergo cell death and release impregnated MSN-Dox, which subsequently induces toxicity towards surrounding glioma cells.

SUBMITTER: Cheng Y

PROVIDER: S-EPMC3879136 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Nanoparticle-programmed self-destructive neural stem cells for glioblastoma targeting and therapy.

Cheng Yu Y Morshed Ramin R Cheng Shih-Hsun SH Tobias Alex A Auffinger Brenda B Wainwright Derek A DA Zhang Lingjiao L Yunis Catherine C Han Yu Y Chen Chin-Tu CT Lo Leu-Wei LW Aboody Karen S KS Ahmed Atique U AU Lesniak Maciej S MS

Small (Weinheim an der Bergstrasse, Germany) 20130721 24

A 3-step glioblastoma-tropic delivery and therapy method using nanoparticle programmed self-destructive neural stem cells (NSCs) is demonstrated in vivo: 1) FDA-approved NSCs for clinical trials are loaded with pH-sensitive MSN-Dox; 2) the nanoparticle conjugates provide a delayed drug-releasing mechanism and allow for NSC migration towards a distant tumor site; 3) NSCs eventually undergo cell death and release impregnated MSN-Dox, which subsequently induces toxicity towards surrounding glioma c ...[more]

PMID: 23873826

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Project description:Extensive cancer research in the past few decades has identified the existence of a rare subpopulation of stem cells in the grove of cancer cells. These cells are known as the cancer stem cells marked by the presence of surface biomarkers, multi-drug resistance pumps and deregulated self-renewal pathways (SRPs). They have a crucial role in provoking cancer cells leading to tumorigenesis and its progressive metastasis. Cancer stem cells (CSCs) are much alike to normal stem cells in their self-renewal mechanisms. However, deregulations in the SRPs are seen in CSCs, making them resistant to conventional chemotherapeutic agents resulting in the tumor recurrence. Current treatment strategies in cancer fail to detect and differentiate the CSCs from their non-tumorigenic progenies owing to absence of specific biomarkers. Now, it has become imperative to understand complex functional biology of CSCs, especially the signaling pathways to design improved treatment strategies to target them. It is hopeful that the SRPs in CSCs offer a promising target to alter their survival strategies and impede their tumorigenic potential. However, there are many perils associated with the direct targeting method by conventional therapeutic agents such as off targets, poor bioavailability and poor cellular distribution. Recent evidences have shown an increased use of small molecule antagonists directly to target these SRPs may lead to severe side-effects. An alternative to solve these issues could be an appropriate nanoformulation. Nanoformulations of these molecules could provide an added advantage for the selective targeting of the pathways especially Hedgehog, Wnt, Notch and B-cell-specific moloney murine leukemia virus integration site 1 in the CSCs while sparing the normal stem cells. Hence, to achieve this goal a complete understanding of the molecular pathways corroborate with the use of holistic nanosystem (nanomaterial inhibition molecule) could possibly be an encouraging direction for future cancer therapy.

Dataset Information

Nanoparticle-programmed self-destructive neural stem cells for glioblastoma targeting and therapy.

Publications

Nanoparticle-programmed self-destructive neural stem cells for glioblastoma targeting and therapy.

Similar Datasets

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