Targeting the Tumor Microenvironment with Fluorescence-Activatable Bispecific Endoglin/Fibroblast Activation Protein...

Area of Science:

• Nanotechnology
• Biomedical Engineering
• Oncology

Background:

• Liposomes are biocompatible nanocarriers for drug and contrast agent delivery.
• Tumor heterogeneity necessitates validated markers for effective targeted delivery.
• Simultaneous targeting of tumor vasculature and fibroblasts shows promise.

Purpose of the Study:

• To develop and validate bispecific liposomes for targeting fibroblast activation protein (FAP) and endoglin.
• To assess the potential of these liposomes for tumor imaging and image-guided surgery.

Main Methods:

• Preparation of fluorescence-quenched liposomes encapsulating DY-676-COOH.
• Incorporation of a non-quenched green fluorescent phospholipid for tracking intact liposomes.
• Coupling of single chain antibody fragments specific for FAP and murine endoglin to the liposomal surface.
• Validation in tumor cells and xenografted mice models.

Main Results:

• Bispecific liposomes demonstrated fluorescence quenching and activatability.
• Selective delivery of encapsulated dye into tumor vessels and fibroblasts was achieved.
• Successful fluorescence imaging of tumors and detection of swollen lymph nodes in mice models.
• Liposomes showed selectivity for target cells.

Conclusions:

• Bispecific liposomes targeting FAP and endoglin are effective for targeted delivery in the tumor microenvironment.
• These liposomes hold potential for advanced tumor imaging and image-guided surgical applications.