Nucleic acid therapeutics: concepts for targeted delivery to solid tumors

Area of Science:

• Biotechnology
• Nanomedicine
• Oncology

Background:

• Solid tumors exhibit common characteristics like hyperproliferation and leaky vasculature, offering targets for macromolecular drug delivery.
• Effective tumor targeting of nucleic acid carriers requires systemic injection compatibility and resistance to enzymatic degradation.
• Current strategies focus on biodegradable and biocompatible carriers to minimize toxic side effects.

Purpose of the Study:

• To develop advanced nucleic acid carriers for targeted delivery to solid tumors.
• To investigate the potential of modified nucleic acids and smart carrier systems for cancer therapy.
• To evaluate the combination of gene therapy and radiotherapy for enhanced antitumoral effects.

Main Methods:

• Nucleic acids were chemically modified for enzymatic resistance.
• Cationic lipids or polycations condensed nucleic acids into virus-like structures.
• Surface modification with hydrophilic polymers and cell-binding ligands facilitated passive and active tumor targeting.
• Thermoresponsive gene carriers were designed for selective accumulation via hyperthermia.
• Antitumoral RNA delivery was tested in an orthotopic brain tumor model.

Main Results:

• Nucleic acid carriers demonstrated resistance to degradation and enabled tumor targeting.
• Thermoresponsive carriers showed selective accumulation in tumors under hyperthermia.
• Tumor-specific delivery of antitumoral RNA was achieved in a brain tumor model.
• Combination therapy with gene and radiotherapy enhanced antitumoral effects and radionuclide accumulation.

Conclusions:

• Smart design of nucleic acid carriers enables effective tumor targeting and delivery.
• Thermoresponsive and ligand-modified carriers offer improved therapeutic strategies.
• Combining advanced nucleic acid delivery with gene and radiotherapy shows promise for treating incurable cancers.