Anti-MicroRNA-21 Oligonucleotide Loaded Spermine-Modified Acetalated Dextran Nanoparticles for B1 Receptor-Targeted...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Targeted delivery of microRNAs (miRNAs) via nanoparticles (NPs) shows promise for cancer therapy.
• The blood-tumor barrier (BTB) poses a significant challenge for treating brain cancers like glioblastoma multiforme (GBM).

Purpose of the Study:

• To develop a novel targeted antisense miRNA-21 oligonucleotide (ATMO-21) delivery system for GBM treatment.
• To overcome the BTB challenge for effective miRNA delivery to brain tumors.

Main Methods:

• Engineered spermine-modified acetalated dextran NPs (SpAcDex NPs) decorated with a bradykinin ligand agonist.
• SpAcDex NPs temporarily open the BTB by activating G-protein-coupled receptors.
• High loading (over 90%) of ATMO-21 into SpAcDex NPs with controlled release in acidic lysosomes.

Main Results:

• SpAcDex NPs enhanced transportation and accumulation of ATMO-21 in tumor sites.
• ATMO-21 induced cell apoptosis and inhibited vascular endothelial growth factor expression by downregulating hypoxia-inducible factor (HIF-1α).
• In vivo studies demonstrated significant inhibition of tumor growth and angiogenesis in an orthotopic U87MG glioma model.

Conclusions:

• Agonist-modified SpAcDex NPs represent a promising strategy for GBM treatment.
• This approach combines targeted gene therapy with antiangiogenic therapy for enhanced efficacy.
• The developed system effectively overcomes the BTB for targeted brain tumor treatment.