Direct Radiolabeling of Trastuzumab-Targeting Triblock Copolymer Vesicles with 89 Zr for Positron Emission Tomography Imaging.
Veronika KozlovskayaMaxwell DucharmeMaksim DolmatJames M OmweriVolkan TekinSuzanne E LapiEugenia KharlampievaPublished in: Biomacromolecules (2023)
Radiolabeled drug nanocarriers that can be easily imaged via positron emission tomography (PET) are highly significant as their in vivo 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 via binding affinity to overexpressed cancer cell receptors is crucial to improve the theranostic delivery to tumors. Herein, we developed 89 Zr-labeled triblock copolymer polymersomes of 60 nm size through chelator-free radiolabeling. The polymersomes are assembled from poly( N -vinylpyrrolidone) 5 - b -poly(dimethylsiloxane) 30 - b -poly( N -vinylpyrrolidone) 5 (PVPON 5 -PDMS 30 -PVPON 5 ) 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 89 Zr radionuclide and targeting recombinant humanized monoclonal antibody, trastuzumab (Tmab). Unlike bare PVPON 5 -PDMS 30 -PVPON 5 polymersomes, TA- and Tmab-modified polymersomes demonstrated a high radiochemical yield of more than 95%. Excellent retention of 89 Zr by the vesicle membrane for up to 7 days was confirmed by PET in vivo imaging. Animal biodistribution using healthy BALB/c mice confirmed the clearance of 89 Zr-labeled polymersomes through the spleen and liver without their accumulation in bone, unlike the free nonbound 89 Zr radiotracer. The 89 Zr-radiolabeled polymersomes were found to specifically target BT474 HER2-positive breast cancer cells via 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.
Keyphrases
- pet imaging
- positron emission tomography
- cancer therapy
- drug delivery
- computed tomography
- monoclonal antibody
- human health
- pet ct
- high resolution
- photodynamic therapy
- drug release
- risk assessment
- type diabetes
- fluorescence imaging
- emergency department
- climate change
- insulin resistance
- mass spectrometry
- capillary electrophoresis