SERS monitoring of photoinduced-enhanced oxidative stress amplifier on Au@carbon dots for tumor catalytic therapy

Abstract

Currently, artificial enzymes-based photodynamic therapy (PDT) is attractive due to its efficient capacity to change the immunosuppressive tumor microenvironment (TME). It is of great significance to study the therapeutic mechanism of novel artificial enzymes in TME through a monitoring strategy and improve the therapeutic effect. In this study, Au@carbon dots (Au@CDs) nanohybrids with a core-shell structure are synthesized, which not only exhibit tunable enzyme-mimicking activity under near-infrared (NIR) light, but also excellent surface-enhanced Raman scattering (SERS) properties. Therefore, Au@CDs show a good capability for monitoring NIR-photoinduced peroxidase-like catalytic processes via a SERS strategy in tumor. Moreover, the Au@CDs deplete glutathione with the cascade catalyzed reactions, thus elevating intratumor oxidative stress amplifying the reactive oxygen species damage based on the NIR-photoinduced enhanced peroxidase and glutathione oxidase-like activities, showing excellent and fast PDT therapeutic effect promoted by photothermal property in 3 min, finally leading to apoptosis in cancer cells. Through SERS monitoring, it is further found that after removing the NIR light source for 33 min, the reactive oxygen species (ROS) activity of the TME is counteracted and eliminated due to the presence of glutathione. This work presents a guidance to rationally design of artificial enzyme for ROS-involved therapeutic strategies and a new spectroscopic tool to evaluate the tumor catalytic therapy.

Fig. 1. Morphology of CDs and Au@CDs.

a The synthesis procedure of the core-shelled Au@CDs nanospheres. b Raman enhancement mechanism of core-shelled nanocomposites. c HRTEM image of initial CDs, d, e TEM image of as-prepared Au@CDs nanospheres, and f HRTEM image of the interface region of Au@CDs.

Fig. 2. Structural characterization of CDs and Au@CDs.

a UV-vis-NIR absorption spectra of CDs and Au@CDs in aqueous solution, (inset: the solution color of (1) CDs and (2) Au@CDs under natural light). XPS spectra of CDs and Au@CDs: b full survey spectrum, c Au 4f, d C 1s, e O 1s, f N 1s. g Photoluminescent spectra (under 340 nm excitation) and h Raman spectra of CDs and Au@CDs in aqueous suspension. i Description of the CT effect in Au@CDs hybrids.

Fig. 3. Photothermal effect evaluation of Au@CDs.

a Mechanism of the photo-thermal process induced by the SPR effect of Au@CDs, b vis-NIR absorbance spectra of Au@CDs in aqueous solution with varied concentrations, c the heating curves of Au@CDs under irradiation of 808 nm laser at varying concentrations in water (laser power: 2 W cm−2), d the heating and cooling curves of Au@CDs for laser on/off and plot of cooling time versus the negative natural logarithm of the temperature driving force.

Fig. 4. Photoinduced enhanced enzyme-like catalytic properties of Au@CDs.

a UV–vis spectra of Au@CDs+ H₂O₂ +TMB systems in darkness or under 808 nm laser irradiation (react for 30 min), b SERS monitoring of Au@CDs+ H₂O₂ +TMB systems in darkness and c under 808 nm laser irradiation. d SERS intensities of peaks at 1611 cm^–1 versus times. e EPR spectra of varied systems: (1) H₂O₂, (2) H₂O₂ + NIR, (3) H₂O₂ + Au@CDs, (4) H₂O₂ + Au@CDs + NIR. DMPO was used as spin adduct and NIR light is from 808 nm laser. f EPR spectra of varied systems: (1) GSH, (2) GSH + NIR, (3) GSH + Au@CDs, (4) GSH + Au@CDs + NIR in aqueous solution and (5) Au@CDs, (6) Au@CDs + NIR, (7) GSH + Au@CDs + NIR in methanol solution. DMPO was used as spin adduct and NIR light is from 808 nm laser. g Possible mechanism for the photoinduced enhanced POD-mimicking activities and h the photo-mediated GSHOx-mimicking activities under 808 nm laser irradiation.

Fig. 5. Therapeutic effect of Au@CDs and SERS monitoring of the catalytic reaction in the TME.

a Treatment schedule for in vivo anti-metastasis study. b Tumor volume and c tumor weight in mice after Au@CDs + H₂O₂ + 808 nm laser treatments (2 W cm⁻²) with different concentration of Au@CDs. d Illustration of Raman studies of intratumor oxidative stress processes. e Time-dependent SERS spectra during the process of oxidative stress in tumor and f time-dependent intensities of the characteristic bands of oxTMB.