Efficient tumor targeting by polysaccharide decked polyethylenimine based nanocomposites.

Area of Science:

• Biomaterials Science
• Gene Therapy
• Nanotechnology

Background:

• Gene therapy requires efficient and targeted delivery vectors.
• Polyethylenimine (PEI) is a common gene delivery vector but suffers from toxicity and low specificity.
• Hyaluronic acid (HA) is a natural polysaccharide that can improve biocompatibility and targeting.

Purpose of the Study:

• To develop and characterize hyaluronic acid-polyethylenimine (HP) nanocomposites for targeted gene delivery to solid tumors.
• To evaluate the transfection efficiency, cytotoxicity, and in vivo tumor targeting of HP nanocomposites.

Main Methods:

• HP nanocomposites were synthesized by blending HA with PEI (25 kDa).
• Characterization included size, morphology, and zeta potential analysis.
• In vitro studies assessed pDNA protection, transfection efficiency in various cell lines (HEK293, HEK293T, HeLa), and cytotoxicity (MTT assay).
• In vivo studies utilized gamma scintigraphy in mice bearing Ehrlich ascites tumor (EAT) to evaluate tumor accumulation.

Main Results:

• HP nanocomposites demonstrated efficient pDNA protection and significantly higher transfection efficiency (1-8 folds) compared to commercial transfection reagents.
• Transfection was effective even in serum-containing media.
• MTT assays revealed improved cell viability in HP nanocomposite-treated cells (HEK293T, HepG2, HeLa).
• In vivo studies showed higher accumulation of HP-4 nanocomposite in solid tumors compared to PEI alone.

Conclusions:

• HP nanocomposites represent a promising platform for site-specific gene therapy.
• Partial charge shielding by HA enhances specificity and reduces toxicity.
• These findings support HP nanocomposites as a viable alternative for targeted delivery in gene therapy.