The In Situ Sulfidation of Cu₂O by Endogenous H₂S for Colon Cancer Theranostics

Abstract

Expression of a high concentration of H2S is closely related to the formation of colon cancer tumors. However, only a few H2S‐triggered theranostics agents for colon cancer have been reported to date. Now, a turn‐on theranostics agent was developed by utilizing the in situ reaction of Cu2O and endogenous H2S at colon tumor sites. Based on in vitro and in vivo experiments, excellent photoacoustic imaging and photothermal therapy were both confirmed by this in situ reaction‐activated colon cancer theranostics method. This work established a simple and efficient strategy for both diagnosis and treatment of colon cancer with a novel trigger mechanism, which provides a new route for colon cancer theranostics based on the in situ reactions at the tumor sites.

Surface Plasmon Resonance–Enhanced Photoacoustic Imaging and Photothermal Therapy of Endogenous H2S‐Triggered Au@Cu2O

“…In contrast, the absorption intensity at 808 nm of triggered Au@Cu 2 O changed significantly even at very low concentrations, NaHS (<0.4 × 10 −3 m ) and Au@Cu 2 O (0.3 × 10 −3 m ) as shown in Figure b and Figure S6d in the Supporting Information. The strong Au@Cu 2 O+NaHS absorbance at low concentration indicated that the injection dose can be reduced to a very low concentration compared with our previous report . The interfering substance, including common ions and amino acids, was used to evaluate the interference factors for the NaHS‐triggered Au@Cu 2 O.…”

“…The other AOAA+Au@Cu 2 O and SAM+Au@Cu 2 O mice were treated one with, aminooxyacetic acid (AOAA, an endogenous H 2 S inhibitor) and the other with S ‐adenosyl‐L‐methionine (SAM, an endogenous H 2 S promoter) prior to intravenous injection of Au@Cu 2 O. In order to demonstrate that the enhanced performance of Au@Cu 2 O as a result of the coupling effect can improve the contrast, the injected dose of Au@Cu 2 O is 2.5 mg kg −1 , which is much lower than 6 mg kg −1 used for Cu 2 O in our previous report . The photoacoustic images of mice were collected before (control) and between 1 and 8 h after treatment (Figure a).…”

“…Tumor Models : The HCT‐116 tumor model was performed following our previous method on the 4–6 weeks BALB/c nude mice . In addition, the use and sacrifice of the mice was approved by the animal ethics committee of Shanghai Normal University and was also in strict accordance with the Institutional Animal Care and Use Committee (IACUC).…”

“…In colon cancer, one of the specific physiological features is the highly expressed endogenous hydrogen sulfide (H 2 S) . Using endogenous H 2 S to trigger the photoacoustic imaging and photothermal therapy function of smart theranostics agents can effectively improve the diagnosis and treatment of colon cancer . For instance, Zhao and co‐workers developed an H 2 S‐triggered smart theranostics agent for NIR‐II fluorescence imaging–guided photothermal therapy .…”

“…However, effective photothermal therapy can only be obtained at a very high‐power density (5.37 W cm −2 ) for these agents. Recently, our group has also developed an H 2 S‐triggered smart agent for photoacoustic imaging and photothermal therapy of colon cancer by utilizing the in situ sulfidation of Cu 2 O with endogenous H 2 S . However, due to its low photothermal conversion performance, additional doses of Cu 2 O are required, which increases its toxic levels.…”