Ionic Coating of siRNA Polyplexes with cRGD–PEG–Hyaluronic Acid To Modulate Serum Stability and In Vivo Performance DOI

Victoria C. Vetter,

Mina Yazdi,

Irene Gialdini

et al.

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Efficient delivery of siRNA-based polyplexes to tumors remains a major challenge. Nonspecific interactions in the bloodstream, limited circulation time, and nontargeted biodistribution hamper sufficient tumor accumulation. To address these challenges, we developed an ionic hyaluronic acid (HA) coating shield sequence-defined oligoaminoamide-based polyplexes. This should positive polyplex surface charge, thus reducing nonspecific enhancing serum stability. Additionally, modified HA with cyclic RGDfK (cRGD) peptide specifically target endothelial cells (TECs). Optionally, polyethylene glycol (PEG) spacer was also introduced improve ligand presentation on surface. The HA-coated exhibited favorable physicochemical properties, including negative zeta potential effective siRNA retention within polyplex, which not adversely affected by PEG or cRGD modification. In vitro analyses revealed that only enhanced cell association preserved high transfection efficiency plain cationic but coating-dependent cellular internalization, as evidenced competitive inhibition experiment. Even presence serum, encapsulated effectively, suitable particle sizes, maintained gene silencing efficiency. vivo studies involving intravenous administration into Neuro2a tumor-bearing mice showed coating, particularly when cRGD, significantly increased accumulation HA–PEG–cRGD-shielded compared Collectively, our results indicate superior performance terms stability uptake, both vivo.

Language: Английский

Ionic Coating of siRNA Polyplexes with cRGD–PEG–Hyaluronic Acid To Modulate Serum Stability and In Vivo Performance DOI

Victoria C. Vetter,

Mina Yazdi,

Irene Gialdini

et al.

Biochemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 18, 2025

Efficient delivery of siRNA-based polyplexes to tumors remains a major challenge. Nonspecific interactions in the bloodstream, limited circulation time, and nontargeted biodistribution hamper sufficient tumor accumulation. To address these challenges, we developed an ionic hyaluronic acid (HA) coating shield sequence-defined oligoaminoamide-based polyplexes. This should positive polyplex surface charge, thus reducing nonspecific enhancing serum stability. Additionally, modified HA with cyclic RGDfK (cRGD) peptide specifically target endothelial cells (TECs). Optionally, polyethylene glycol (PEG) spacer was also introduced improve ligand presentation on surface. The HA-coated exhibited favorable physicochemical properties, including negative zeta potential effective siRNA retention within polyplex, which not adversely affected by PEG or cRGD modification. In vitro analyses revealed that only enhanced cell association preserved high transfection efficiency plain cationic but coating-dependent cellular internalization, as evidenced competitive inhibition experiment. Even presence serum, encapsulated effectively, suitable particle sizes, maintained gene silencing efficiency. vivo studies involving intravenous administration into Neuro2a tumor-bearing mice showed coating, particularly when cRGD, significantly increased accumulation HA–PEG–cRGD-shielded compared Collectively, our results indicate superior performance terms stability uptake, both vivo.

Language: Английский

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