A chelator-free multifunctional [64Cu]CuS nanoparticle platform for simultaneous micro-PET/CT imaging and photothermal ablation therapy

Abstract

We synthesized and evaluated a novel class of chelator-free [(64)Cu]CuS nanoparticles (NPs) suitable both for PET imaging and as photothermal coupling agents for photothermal ablation. These [(64)Cu]CuS NPs are simple to make, possess excellent stability, and allow robust noninvasive micro-PET imaging. Furthermore, the CuS NPs display strong absorption in the near-infrared (NIR) region (peak at 930 nm); passive targeting prefers the tumor site, and mediated ablation of U87 tumor cells occurs upon exposure to NIR light both in vitro and in vivo after either intratumoral or intravenous injection. The combination of small diameter (∼11 nm), strong NIR absorption, and integration of (64)Cu as a structural component makes these [(64)Cu]CuS NPs ideally suited for multifunctional molecular imaging and therapy.

Figure 1

Characterization of CuS NPs. (A) TEM image of PEG-CuS NPs. Inset: particle size distribution. (B) Absorption spectra of Cit-CuS NPs and PEG-CuS NPs.

Figure 2

Pharmacokinetic profiles of Cit-CuS NPs (n = 3) and PEG-CuS NPs (n = 5) following intravenous administration in mice (A); and biodistribution (B) of Cit-CuS NPs (n = 5) and PEG-CuS NPs (n = 5) at 24 h after intravenous injection in mice bearing subcutaneous U87 glioma xenografts. Data represent mean ± standard deviation.

Figure 3

Micro-PET/CT images of nude mice-bearing s.c. U87 glioma xenografts acquired at 1, 6, and 24 h after i.v. injection of PEG-[⁶⁴Cu]-CuS NPs. Yellow arrow: tumor; orange arrow: bladder; Red arrow: standard.

Figure 4

PEG-CuS NPs acted as an efficient photothermal coupling agent. (A) Temperature elevation over a period of 9 min of exposure to NIR light (16 W/cm²) at various PEG-CuS NP concentrations. Water was used as control. (B) Temperature change (ΔT) over a period of 9 min as a function of PEG-CuS NP concentration expressed as CuS molecular units.

Figure 5

PEG-CuS NPs induced photothermal destruction of U87 tumors in vivo. (A). Photographs of tumor-bearing mice before and at 24 h after NIR laser irradiation (12 W/cm² at 808 nm for 5 min). (B). Representative microphotograph of tumors removed at 24 h after NIR laser treatment. The tissues were cryosectioned into 5 µm slices and stained with H&E. Bar, top, 200 µm; Bar, bottle, 20 µm. (C). Quantitative analysis of percentage of necrosis zone induced by various treatments. The data were measured as a percentage of the whole tumor area. Asterisk indicates statistic significance compared to the no-treatment control (p = 0.006). Error bars, standard deviation (n = 5). NPs, CuS nanoparticles; NIR, near-infrared laser; T, tumor.