Versatile Supermolecular Inclusion Complex Based on Host-Guest Interaction for Targeted Gene Delivery.

Area of Science:

• Biomaterials Science
• Gene Therapy
• Nanotechnology

Background:

• Developing effective and targeted gene delivery systems is crucial for cancer therapy.
• Polyethylenimine (PEI) is a common non-viral gene vector, but its targeting efficiency needs improvement.
• β-cyclodextrin (CD) and adamantyl peptide (AdGRGDS) can be utilized for targeted modifications.

Purpose of the Study:

• To create a targeted gene delivery system by conjugating β-cyclodextrin modified polyethylenimine (PEI-CD) with adamantyl peptide (AdGRGDS).
• To evaluate the DNA binding, nanoparticle formation, in vitro and in vivo transfection efficiency, and tumor-targeting specificity of the developed system.

Main Methods:

• Host-guest interaction was used to conjugate PEI-CD and AdGRGDS.
• DNA binding capability and nanoparticle formation were assessed.
• In vitro transfection efficiency was evaluated in HeLa and COS7 cells using luciferase assays.
• Cellular uptake and targeting specificity were studied using confocal laser scanning microscopy (CLSM) and flow cytometry.
• In vivo studies were conducted in a rat model with hepatic carcinoma (H22 cells) via subcutaneous and tail-vein injections.

Main Results:

• PEI-CD/AdGRGDS exhibited excellent DNA binding and formed uniform spherical nanoparticles.
• In vitro, PEI-CD/AdGRGDS showed enhanced gene expression in HeLa cells compared to PEI-CD.
• CLSM and flow cytometry confirmed good targeting specificity of PEI-CD/AdGRGDS to tumor cells overexpressing integrin αvβ3.
• In vivo, PEI-CD/AdGRGDS demonstrated stronger gene expression efficiency and targeted distribution to tumor xenografts compared to PEI-CD.

Conclusions:

• The PEI-CD/AdGRGDS system effectively delivers genes with high targeting specificity to tumors expressing integrin αvβ3.
• The GRGDS peptide moiety is key for achieving tumor cell targeting.
• This novel gene delivery system holds significant promise for targeted cancer therapy.