Engineered smart materials for RNA based molecular therapy to treat Glioblastoma

Glioblastoma (GBM) is an aggressive malignancy of the central nervous system (CNS) that remains incurable despite the multitude of improvements in cancer therapeutics. The conventional chemo and radiotherapy post-surgery have only been able to improve the prognosis slightly; however, the development...

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Main Authors: Ravi Raj Singh, Indranil Mondal, Taskeen Janjua, Amirali Popat, Ritu Kulshreshtha
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2024-03-01
Series:Bioactive Materials
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2452199X23003560
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author Ravi Raj Singh
Indranil Mondal
Taskeen Janjua
Amirali Popat
Ritu Kulshreshtha
author_facet Ravi Raj Singh
Indranil Mondal
Taskeen Janjua
Amirali Popat
Ritu Kulshreshtha
author_sort Ravi Raj Singh
collection DOAJ
description Glioblastoma (GBM) is an aggressive malignancy of the central nervous system (CNS) that remains incurable despite the multitude of improvements in cancer therapeutics. The conventional chemo and radiotherapy post-surgery have only been able to improve the prognosis slightly; however, the development of resistance and/or tumor recurrence is almost inevitable. There is a pressing need for adjuvant molecular therapies that can successfully and efficiently block tumor progression. During the last few decades, non-coding RNAs (ncRNAs) have emerged as key players in regulating various hallmarks of cancer including that of GBM. The levels of many ncRNAs are dysregulated in cancer, and ectopic modulation of their levels by delivering antagonists or overexpression constructs could serve as an attractive option for cancer therapy. The therapeutic potential of several types of ncRNAs, including miRNAs, lncRNAs, and circRNAs, has been validated in both in vitro and in vivo models of GBM. However, the delivery of these RNA-based therapeutics is highly challenging, especially to the tumors of the brain as the blood-brain barrier (BBB) poses as a major obstacle, among others. Also, since RNA is extremely fragile in nature, careful considerations must be met while designing a delivery agent. In this review we have shed light on how ncRNA therapy can overcome the limitations of its predecessor conventional therapy with an emphasis on smart nanomaterials that can aide in the safe and targeted delivery of nucleic acids to treat GBM. Additionally, critical gaps that currently exist for successful transition from viral to non-viral vector delivery systems have been identified. Finally, we have provided a perspective on the future directions, potential pathways, and target areas for achieving rapid clinical translation of, RNA-based macromolecular therapy to advance the effective treatment of GBM and other related diseases.
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spelling doaj.art-45593be6dc9945f88898f6d02980024f2023-11-28T04:06:16ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2024-03-0133396423Engineered smart materials for RNA based molecular therapy to treat GlioblastomaRavi Raj Singh0Indranil Mondal1Taskeen Janjua2Amirali Popat3Ritu Kulshreshtha4Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, India; School of Pharmacy, The University of Queensland, Brisbane, QLD, 4072, Australia; University of Queensland –IIT Delhi Academy of Research (UQIDAR)Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, IndiaSchool of Pharmacy, The University of Queensland, Brisbane, QLD, 4072, AustraliaSchool of Pharmacy, The University of Queensland, Brisbane, QLD, 4072, Australia; Department of Functional Materials and Catalysis, Faculty of Chemistry, University of Vienna, Währinger Straße 42, 1090 Vienna, Austria; Corresponding author.Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, India; Corresponding author.Glioblastoma (GBM) is an aggressive malignancy of the central nervous system (CNS) that remains incurable despite the multitude of improvements in cancer therapeutics. The conventional chemo and radiotherapy post-surgery have only been able to improve the prognosis slightly; however, the development of resistance and/or tumor recurrence is almost inevitable. There is a pressing need for adjuvant molecular therapies that can successfully and efficiently block tumor progression. During the last few decades, non-coding RNAs (ncRNAs) have emerged as key players in regulating various hallmarks of cancer including that of GBM. The levels of many ncRNAs are dysregulated in cancer, and ectopic modulation of their levels by delivering antagonists or overexpression constructs could serve as an attractive option for cancer therapy. The therapeutic potential of several types of ncRNAs, including miRNAs, lncRNAs, and circRNAs, has been validated in both in vitro and in vivo models of GBM. However, the delivery of these RNA-based therapeutics is highly challenging, especially to the tumors of the brain as the blood-brain barrier (BBB) poses as a major obstacle, among others. Also, since RNA is extremely fragile in nature, careful considerations must be met while designing a delivery agent. In this review we have shed light on how ncRNA therapy can overcome the limitations of its predecessor conventional therapy with an emphasis on smart nanomaterials that can aide in the safe and targeted delivery of nucleic acids to treat GBM. Additionally, critical gaps that currently exist for successful transition from viral to non-viral vector delivery systems have been identified. Finally, we have provided a perspective on the future directions, potential pathways, and target areas for achieving rapid clinical translation of, RNA-based macromolecular therapy to advance the effective treatment of GBM and other related diseases.http://www.sciencedirect.com/science/article/pii/S2452199X23003560Glioblastoma (GBM)Non-coding RNAs (ncRNA)Nucleic acid therapyOligonucleotide therapyNanocarriersNanoparticles
spellingShingle Ravi Raj Singh
Indranil Mondal
Taskeen Janjua
Amirali Popat
Ritu Kulshreshtha
Engineered smart materials for RNA based molecular therapy to treat Glioblastoma
Bioactive Materials
Glioblastoma (GBM)
Non-coding RNAs (ncRNA)
Nucleic acid therapy
Oligonucleotide therapy
Nanocarriers
Nanoparticles
title Engineered smart materials for RNA based molecular therapy to treat Glioblastoma
title_full Engineered smart materials for RNA based molecular therapy to treat Glioblastoma
title_fullStr Engineered smart materials for RNA based molecular therapy to treat Glioblastoma
title_full_unstemmed Engineered smart materials for RNA based molecular therapy to treat Glioblastoma
title_short Engineered smart materials for RNA based molecular therapy to treat Glioblastoma
title_sort engineered smart materials for rna based molecular therapy to treat glioblastoma
topic Glioblastoma (GBM)
Non-coding RNAs (ncRNA)
Nucleic acid therapy
Oligonucleotide therapy
Nanocarriers
Nanoparticles
url http://www.sciencedirect.com/science/article/pii/S2452199X23003560
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