Engineered RBC-derived nanovesicles functionalized with tumor-targeting ligands: A comparative study on breast cancer...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Cell membrane-derived nanovesicles, especially red blood cell nanovesicles (RNVs), show promise for cancer drug delivery due to biocompatibility and immune evasion.
• However, poor tumor targeting and biodistribution limit their clinical application.

Purpose of the Study:

• To functionalize RNVs with various tumor-targeting ligands (cRGD, transferrin, folic acid, GE11, RVG29).
• To compare the tumor-homing efficiency, biodistribution, and biosafety of these engineered RNVs in a breast cancer model.

Main Methods:

• Functionalization of RNVs with cRGD, transferrin (TRF), folic acid (FA), GE11, and RVG29 ligands.
• In vitro and in vivo evaluation of tumor targeting, accumulation, and cellular uptake.
• Biodistribution and biosafety assessment in murine models using fluorescence imaging.

Main Results:

• Engineered RNVs demonstrated significantly enhanced tumor affinity compared to unmodified RNVs.
• RNV@cRGD exhibited the highest intratumoral accumulation and cellular uptake, followed by RNV@GE11, RNV@TRF, RNV@FA, and RNV@RVG29.
• All functionalized RNVs showed good stability, tumor selectivity, and negligible toxicity in vivo.

Conclusions:

• cRGD is identified as the most effective ligand for targeting breast cancer using RNVs.
• This study provides design principles for developing targeted RNV-based drug delivery systems.
• Ligand-engineered RNVs hold significant translational potential for clinical oncology applications.