Prostate cancer cell-specific VEGF siRNA delivery system using cell targeting peptide conjugated polyplexes

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Biology

Background:

• Prostate cancer remains a significant health concern, necessitating advanced therapeutic strategies.
• Targeted gene delivery systems are crucial for enhancing therapeutic efficacy and minimizing off-target effects.
• Vascular Endothelial Growth Factor (VEGF) plays a critical role in tumor angiogenesis and progression.

Purpose of the Study:

• To develop a target-specific polymeric gene carrier for delivering VEGF small interfering RNA (siRNA) to prostate cancer cells.
• To evaluate the efficiency of the developed carrier in gene silencing and cellular uptake.
• To assess the stability and specificity of the gene delivery system.

Main Methods:

• Conjugation of prostate cancer-binding peptide (PCP) with polyethylenimine (PEI) via a poly(ethylene glycol) (PEG) linker to form PEI-PEG-PCP.
• Condensation of VEGF siRNA with PEI-PEG-PCP to form stable polyelectrolyte complexes (polyplexes).
• Assessment of polyplex size, VEGF inhibition efficiency in PC-3 cells, and cellular uptake via confocal microscopy.

Main Results:

• PEI-PEG-PCP effectively condensed siRNA into stable polyplexes (~150 nm).
• VEGF siRNA/PEI-PEG-PCP polyplexes demonstrated significantly higher VEGF inhibition in PC-3 cells compared to unmodified carriers.
• Enhanced gene silencing was maintained under serum conditions due to PEG stabilization.
• Confocal microscopy confirmed PCP ligand-specific delivery of polyplexes into PC-3 cells.

Conclusions:

• The PEI-PEG-PCP conjugate serves as an effective and target-specific gene carrier for VEGF siRNA in prostate cancer.
• The developed system shows potential for enhanced gene therapy in prostate cancer treatment.
• The PCP ligand facilitates specific cellular uptake, improving delivery efficiency.