A facile modular approach toward multifunctional supramolecular polyplexes for targeting gene delivery

Area of Science:

• Biomaterials Science
• Nanotechnology
• Gene Therapy

Background:

• Developing safe and efficient gene carriers is crucial for gene therapy.
• Overcoming extra- and intracellular barriers remains a significant challenge.
• Fabricating gene carriers with multiple functionalities is complex.

Purpose of the Study:

• To design a facile, modular approach for targeted, multifunctional gene delivery systems.
• To create a self-assembling gene carrier platform using host-guest interactions.
• To demonstrate the efficacy of customized building blocks for specific barriers.

Main Methods:

• Synthesis and characterization of adamantyl-terminated targeting modules (Ad-RGD, FA-PEG-Ad, LA-PEG-Ad).
• Post-functionalization of adamantyl-decorated cationic poly(ethyleneimine) (PEI-Ad4) with poly(β-cyclodextran) (PCD) and DNA.
• Assembly of supramolecular polyplexes via host-guest interactions between adamantyl and cyclodextrin units.

Main Results:

• Successfully synthesized and characterized three targeting guest modules.
• Created multifunctional supramolecular polyplexes capable of targeted gene delivery.
• Demonstrated enhanced cellular uptake and transfection activity in receptor-positive cells.

Conclusions:

• The modular approach enables rational design of customized gene carriers.
• Supramolecular self-assembly via host-guest interactions provides a versatile platform.
• This strategy holds promise for targeted gene delivery in various tissues and cells.