Anti-angiogenic nanotherapy via active targeting systems to tumors and adipose tissue vasculature

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Sophisticated drug delivery systems (DDS) are crucial for delivering therapeutics, especially macromolecules like nucleic acids and proteins, to specific action sites.
• Selective tissue targeting is a prerequisite for future DDS design to maximize efficacy and minimize off-target effects.

Purpose of the Study:

• To review and highlight advanced DDS strategies for actively targeting tumor and adipose vasculature.
• To present novel approaches for enhancing tissue selectivity and therapeutic payload delivery in vivo.

Main Methods:

• Development of a dual-targeting strategy combining receptor-specific ligands and cell-penetrating peptides for tumor vasculature targeting.
• Design of a pH-sensitive cationic lipid for enhanced endosomal release and improved blood stability of encapsulated siRNA.
• Utilizing prohibitin-targeted nanoparticles (PTNP) with PEGylated nanoparticles functionalized with KGGRAKD peptides for adipose vasculature targeting.

Main Results:

• Dual-targeting strategy demonstrated synergistic enhancement of tissue selectivity in vivo.
• pH-sensitive cationic lipid improved siRNA endosomal escape and systemic stability.
• PTNP selectively targeted adipose vasculature, delivering Cytochrome c (CytC) to endothelial cells and inducing anti-obese effects and apoptosis.
• Enhanced permeability and retention (EPR) effect observed in adipose vasculature, particularly in obese mice, facilitating nanoparticle extravasation.

Conclusions:

• Active targeting strategies significantly enhance the selectivity of DDS for tumor and adipose tissues.
• These advancements in targeted DDS pave the way for expanded applications of nanomedicines.
• The observed EPR effect in adipose tissue suggests potential for passive targeting strategies in this context as well.