Assessment of CCR5 targeted nanotripod for breast cancer photothermal therapy

Objectives This study was to assess the capability of a novel CuPd@Au core-shell nanotripod for PET imaging guided photothermal therapy in a triple negative breast cancer (TNBC) mouse model using a CCR5 targeting peptide DAPTA.

Methods The targeted 64CuPd@Au-PEG-DAPTA core-shell nanotripods were prepared through direct incorporation of 64Cu into the nanostructure for CCR5 imaging. Biodistribution, PET, and photothermal treatment were performed at two weeks post injection in the 4T1 TNBC model. Biological characterization of CCR5 was done in tumors after imaging. Competitive receptor blocking studies were also performed to confirm targeting specificity.

Results PET imaging with 64CuPd@Au-PEG-DAPTA showed significantly higher tumor uptake (SUV= 2.18±0.16, n=3) than the non-targeted nanotripods (64CuPd@Au-PEG) in the 4T1 tumor-bearing mice (1.47±0.16, p<0.01, n=3). Competitive blocking studies significantly reduced tumor uptake of targeted nanotripods (SUV=1.59±0.05, p<0.005, n=3). The elevated expression of CCR5 in tumors was confirmed, which led to 60% less injected dose of 64CuPd@Au-PEG-DAPTA to achieve sufficient amount (0.47 mg) necessary for photothermal treatment. The targeted nanotripods demonstrated a 3 times temperature increase (21.8 °C) in tumors than in the saline treated group (5.7 °C). 18F-FDG PET showed 5 times less uptake in 64CuPd@Au-PEG-DAPTA treated group (0.13±0.02, n=3) compared to the saline group (0.82±0.21, p< 0.001, n=3).

Conclusions This novel core-shell nanotripod demonstrated its optimal physicochemical properties as an imaging agent and photothermal transducer for cancer theranostics. PET imaging showed specific targeting of CCR5 up-regulated in mouse 4T1 TNBC tumors. The targeted treatment following PET guidance indicated the potential of 64CuPd@Au-PEG-DAPTA for image-guided cancer treatment.