Direct Radiolabeling of Trastuzumab-Targeting Triblock Copolymer Vesicles with Zr for Positron Emission Tomography Imaging.

Radiolabeled drug nanocarriers that can be easily imaged positron emission tomography (PET) are highly significant as their outcome can be quantitatively PET-traced with high sensitivity. However, typical radiolabeling of most PET-guided theranostic vehicles utilizes modification with chelator ligands, which presents various challenges. In addition, unlike passive tumor targeting, specific targeting of drug delivery vehicles binding affinity to overexpressed cancer cell receptors is crucial to improve the theranostic delivery to tumors. Herein, we developed Zr-labeled triblock copolymer polymersomes of 60 nm size through chelator-free radiolabeling. The polymersomes are assembled from poly(-vinylpyrrolidone)--poly(dimethylsiloxane)--poly(-vinylpyrrolidone) (PVPON-PDMS-PVPON) triblock copolymers followed by adsorption of a degradable tannin, tannic acid (TA), on the polymersome surface through hydrogen bonding. TA serves as an anchoring layer for both Zr radionuclide and targeting recombinant humanized monoclonal antibody, trastuzumab (Tmab). Unlike bare PVPON-PDMS-PVPON polymersomes, TA- and Tmab-modified polymersomes demonstrated a high radiochemical yield of more than 95%. Excellent retention of Zr by the vesicle membrane for up to 7 days was confirmed by PET imaging. Animal biodistribution using healthy BALB/c mice confirmed the clearance of Zr-labeled polymersomes through the spleen and liver without their accumulation in bone, unlike the free nonbound Zr radiotracer. The Zr-radiolabeled polymersomes were found to specifically target BT474 HER2-positive breast cancer cells the Tmab-TA complex on the vesicle surface. The noncovalent Tmab anchoring to the polymersome membrane can be highly advantageous for nanoparticle modification compared to currently developed covalent methods, as it allows easy and quick integration of a broad range of targeting proteins. Given the ability of these polymersomes to encapsulate and release anticancer therapeutics, they can be further expanded as precision-targeted therapeutic carriers for advancing human health through highly effective drug delivery strategies.