Nucleic acid based therapeutics for tumor therapy

Area of Science:

• Biomedical Engineering
• Molecular Biology
• Oncology

Background:

• Cancer is a heterogeneous disease with unique features exploitable for macromolecular therapeutics.
• Tumor cell proliferation, vasculature, and leaky vessels facilitate targeted delivery of nucleic acids.
• Polycationic gene carriers (polyplexes) are developed for nucleic acid delivery, with enhanced understanding of cellular interactions.

Purpose of the Study:

• To explore the potential of polycationic gene carriers for targeted cancer therapy.
• To investigate the incorporation of virus-like domains to enhance polyplex functionality.
• To evaluate physical targeting strategies for improving nucleic acid transfer efficiency.

Main Methods:

• Development of polycationic gene carriers (polyplexes) for nucleic acid delivery.
• Incorporation of virus-like domains: hydrophilic shielding, targeting ligands, and membrane-active peptides.
• Application of physical targeting methods: locoregional hyperthermia and photochemical internalization (PCI).

Main Results:

• Demonstrated successful targeted delivery of nucleic acids into tumor tissues.
• Showcased enhanced cellular uptake and intracellular trafficking via modified polyplexes.
• Achieved eradication of intracranial glioblastoma in mouse models using local double-stranded RNA application.
• Reported promising initial results for a gene-directed enzyme prodrug approach for cyclophosphamide activation.

Conclusions:

• Polycationic gene carriers with incorporated virus-like domains show promise for cancer therapy.
• Physical targeting strategies significantly enhance the efficiency of nucleic acid delivery.
• Therapeutic strategies involving nucleic acids and gene-directed enzyme prodrugs offer potential for cancer treatment.