Facile Synthesis of ⁶⁴Cu‐Doped Au Nanocages for Positron Emission Tomography Imaging

Abstract

This article reports a simple and reliable approach to the synthesis of Cu‐doped Au nanocages through the co‐deposition of Au and Cu on the surfaces (both outer and inner) of pre‐synthesized Au nanocages by reducing HAuCl4 and CuCl2 with ascorbic acid under alkaline conditions. By controlling the total amount of Au and Cu deposited and/or the molar ratio between these two metals, we were able to adjust the Cu content in the resultant Au nanocages. The localized surface plasmon resonance properties of the Cu‐doped Au nanocages resemble those of the conventional Au nanocages, with strong and tunable absorption in the near‐infrared region. When radioactive 64CuCl2 was used in combination with nonradioactive CuCl2 as a source to elemental Cu, we obtained 64Cu‐doped Au nanocages. The radioactive nanocages could serve as tracers for position emission tomography (PET) imaging, and they were found to accumulate effectively in both 4T1 and patient derived xenograft (PDX) tumor models due to the enhanced permeability and retention effect. Autoradiography analysis indicated a homogeneous intra‐tumoral distribution for these nanocages. Taken together, the 64Cu‐doped Au nanocages are promising for image‐guided cancer theranostics.

Gold nanocages for effective photothermal conversion and related applications

“…As such, they can be potentially used for imaging-guided therapy to achieve enhanced treatment efficiency. [62][63][64] This type of nanomaterials with multi-functional properties including imaging, drug delivery, controlled release, and photothermal therapy will be of great interest in nanomedicine.…”

“…7,67 Alternatively, other metals can be post-deposited on the surface of AuNCs through seed-mediated growth to offer additional function or capability. For example, radioactive 64 Cu can be incorporated into the walls of AuNCs through the co-reduction of HAuCl 4 , CuCl 2 , and 64 CuCl 2 in the presence of AuNCs. 64 The radiolabeled nanocages can then be employed as contrast agents for positron emission tomography (PET).…”

“…For example, radioactive 64 Cu can be incorporated into the walls of AuNCs through the co-reduction of HAuCl 4 , CuCl 2 , and 64 CuCl 2 in the presence of AuNCs. 64 The radiolabeled nanocages can then be employed as contrast agents for positron emission tomography (PET). Similarly, the nanocages can be endowed with catalytic ability through the deposition of precious metals such as Pd and Pt.…”

Radiolabeling strategies and pharmacokinetic studies for metal based nanotheranostics

“…In case of hetero‐radionuclides, the MNP core cation and the radionuclide are different, such as doping AuNPs with 64 Cu (Frellsen et al, 2016; Hu, Huang, et al, 2014; Y. Zhao, Detering, et al, 2016; Y. Zhao et al, 2014), AuNPs with 111 In (Ng et al, 2014), AgNPs with 131 I (Sakr et al, 2018), IONPs with 68 Ga (Juan Pellico et al, 2016), AuNCs with 64 Cu (Ye et al, 2018), GdF 3 NPs with 90 Y (Paik et al, 2015), and CuS NPs with 64 Cu (H. Cai et al, 2018; Chakravarty et al, 2016; M. Zhou et al, 2010; M. Zhou et al, 2015). A typical example of such radiochemical doping methods is illustrated in Figure 6 (M. Yang et al, 2017). For radiolabeling, a trace amount of 64 CuCl 2 was added to the mixture of HAuCl 4 and CuCl 2 , which was reduced onto the AuNCs by ascorbic acid in the presence of NaOH and PVP for surface‐coating, that was then replaced with methoxy‐PEG 2k ‐SH.…”

“…Schematic synthesis of 64 Cu‐doped Au nanocages via co‐deposition of Au and Cu atoms on the pre‐synthesized Au nanocages and subsequent 64 Cu‐labeling through radiochemical doping technique (Reprinted with permission from M. Yang et al (2017) with permission. Copyright 2016, John Wiley and Sons)…”