A tissue factor targeted nanomedical system for thrombi-specific drug delivery

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Molecular Biology

Background:

• Tissue factor (TF) is a key initiator of the coagulation cascade, found on damaged endothelium, atherosclerotic plaques, and tumor vasculature.
• Targeting TF is a promising strategy for localized therapies and diagnostics in various diseases.

Purpose of the Study:

• To develop and characterize a novel nanomedical system for targeted delivery to TF-expressing cells.
• To evaluate the targeting efficiency, pharmacokinetics, and safety of the developed nanomedical system.

Main Methods:

• Expression and purification of TF-targeting protein EGFP-EGF1.
• Conjugation of EGFP-EGF1 to PEG-PLGA nanoparticles to form EGF1-EGFP-NP.
• In vitro evaluation of cellular uptake in TF-overexpressing cells (BCEC).
• Pharmacokinetic studies and in vivo imaging in a cortex infarction model.
• Confocal microscopy, Transmission Electron Microscopy (TEM), in vitro cell viability, and in vivo coagulation assays.

Main Results:

• The EGF1-EGFP-NP system was successfully synthesized and characterized.
• EGF1-EGFP-NP demonstrated specific uptake by TF-overexpressing BCEC via EGF1/TF-mediated endocytosis.
• The nanomedical system exhibited similar blood circulation time to non-targeted nanoparticles (NP).
• Enhanced accumulation of EGF1-EGFP-NP was observed in the cortex infarction region.
• EGF1-EGFP-NP effectively bound to TF and translocated through damaged endothelium.
• In vitro and in vivo studies confirmed the safety of the EGF1-EGFP-NP system.

Conclusions:

• The developed EGF1-EGFP-NP nanomedical system shows high targeting efficiency for TF.
• This targeted nanomedicine is safe and demonstrates potential for enhanced accumulation at disease sites.
• EGF1-EGFP-NP holds promise for future applications in TF-related disease treatment and diagnostics.