Engineered smart materials for RNA based molecular therapy to treat Glioblastoma

Ravi Raj Singh; Indranil Mondal; Taskeen Janjua; Amirali Popat; Ritu Kulshreshtha

doi:10.1016/j.bioactmat.2023.11.007

Engineered smart materials for RNA based molecular therapy to treat Glioblastoma

Bioact Mater. 2023 Nov 27:33:396-423. doi: 10.1016/j.bioactmat.2023.11.007. eCollection 2024 Mar.

Authors

Ravi Raj Singh^{1

2

3}, Indranil Mondal¹, Taskeen Janjua², Amirali Popat^{2

4}, Ritu Kulshreshtha¹

Affiliations

¹ Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi, India.
² School of Pharmacy, The University of Queensland, Brisbane, QLD, 4072, Australia.
³ University of Queensland -IIT Delhi Academy of Research (UQIDAR).
⁴ Department of Functional Materials and Catalysis, Faculty of Chemistry, University of Vienna, Währinger Straße 42, 1090 Vienna, Austria.

Abstract

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.

Keywords: Gene therapy; Glioblastoma (GBM); Nanocarriers; Nanoparticles; Non-coding RNAs (ncRNA); Nucleic acid therapy; Oligonucleotide therapy; RNA delivery system.