Integrin αvβ3-Targeted [64Cu]CuS Nanoparticles for PET/CT Imaging and Photothermal Ablation Therapy

  • Bioconjug Chem. 2018 Dec 19;29(12):4062-4071. doi: 10.1021/acs.bioconjchem.8b00690.
Lili Cui  1 ,  Chiyi Xiong  2 ,  Min Zhou  2  3 ,  Sixiang Shi  2 ,  Diana S-L Chow  1 ,  Chun Li  2
Affiliations
  • 1. Department of Pharmacological and Pharmaceutical Sciences , College of Pharmacy, University of Houston , Houston , Texas 77024 , United States.
  • 2. Department of Cancer Systems Imaging , The University of Texas MD Anderson Cancer Center , Houston , Texas 77054-1907 , United States.
  • 3. Institute of Translational Medicine, School of Medicine , Zhejiang University , Hangzhou , 310029 , China.
PMID: 30404438 DOI: 10.1021/acs.bioconjchem.8b00690
Abstract

Copper sulfide (CuS) nanoparticles have been considered one of the most clinical relevant nanosystems because of their straightforward chemistry, small particle size, low toxicity, and intrinsic theranostic characteristics. In our previous studies, radioactive [64Cu]CuS nanoparticles were successfully developed to be used as efficient radiotracers for positron emission tomography and for photothermal ablation therapy of Cancer cells using near-infrared laser irradiation. However, the major challenge of CuS nanoparticles as a theranostic platform is the lack of a means for effective targeted delivery to the tumor site. To overcome this challenge, we designed and synthesized angiogenesis-targeting [64Cu]CuS nanoparticles, which are coupled with cyclic RGDfK peptide [c(RGDfK)] through polyethylene glycol (PEG) linkers using click chemistry. In assessing their tumor-targeting efficacy, we found that the tumor uptakes of [64Cu]CuS-PEG-c(RGDfK) nanoparticles at 24 h after intravenous injection were significantly greater (8.6% ± 1.4% injected dose/gram of tissue) than those of nontargeted [64Cu]CuS-PEG nanoparticles (4.3% ± 1.2% injected dose/gram of tissue, p < 0.05). Irradiation of tumors in mice administered [64Cu]CuS-PEG-c(RGDfK) nanoparticles induced 98.7% necrotic areas. In contrast, irradiation of tumors in mice administered nontargeted CuS-PEG nanoparticles induced 59% necrotic areas ( p < 0.05). The angiogenesis-targeting [64Cu]CuS nanoparticles may serve as a promising platform for image-guided ablation therapy with high efficacy and minimal side effects in future clinical translation of this novel class of multifunctional nanomaterials.

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