Lipid nanoparticle-mediated gene silencing as a targeted therapeutic strategy for glioblastoma multiforme

Abstract

Background: Glioblastoma multiforme is one of the most prevalent primary brain neoplasms worldwide and is associated with high mortality rates. This scenario largely results from tumor heterogeneity, limited therapeutic options, and the difficulty of drug penetration into the central nervous system due to the presence of the blood–brain barrier. Nanovectorization strategies, using techniques such as liposomes and lipid nanoparticles carrying nucleic acids for the silencing of oncogenic genes and microRNAs, have emerged as a promising alternative to improve permeability across this barrier, enhance therapeutic activity within the tumor microenvironment, and consequently prolong patient survival. Objective: To evaluate the efficacy of lipid nanoparticles as targeted drug delivery systems for glioblastoma treatment, as well as their therapeutic mechanisms through gene silencing mediated by RNA interference (RNAi) in in vivo models. Methods: A qualitative literature review was conducted using the PubMed database, including studies published within the last 10 years. The search strategy utilized Boolean operators: (“Liposomes” OR “Nanoparticles”) AND “Central Nervous System” AND “Glioblastoma” AND “Pharmacokinetics” AND “Blood Brain Barrier”. A total of 20 articles were initially identified, of which two were included after eligibility criteria were applied. These criteria required the use of experimental in vivo models (syngeneic and orthotopic) and RNA interference–based gene silencing strategies via lipid-based particles. Results: Nanovectorization of interfering nucleic acids in structures such as liposomes stabilized with gold molecules or lipid nanoparticles containing longer glycolipid anchors promoted a reduction in the post-transcriptional expression of oncogenic microRNAs relevant to tumor viability, such as miRNA-92b, in murine glioblastoma models. This effect was associated with increased cerebral accumulation of therapeutic compounds and enhanced bioavailability in target tissues, resulting from the ability of these nanomolecules to cross the blood–brain barrier and promote cellular internalization. At the systemic level, increased stability of therapeutic nucleic acids during bloodstream transport was also observed due to lipid encapsulation, which protected RNAs from degradation by circulating nucleases and reduced renal clearance of the molecules of interest. Consequently, this process increased their half-life and enhanced the antitumor therapeutic effect. Conclusion: The analysis of the selected studies indicates that lipid nanoparticles used as targeted delivery systems represent a relevant strategy in the field of neuro-oncology. Their ability to cross the blood–brain barrier, increase the stability and bioavailability of therapeutic nucleic acids, and promote the silencing of oncogenic genes in in vivo models makes these complexes particularly promising for the development of increasingly effective therapeutic strategies for the treatment of central nervous system tumors.