Introduction

Cervical cancer is the second most common malignant tumor in women worldwide and has a high mortality rate, especially when it is associated with human papillomavirus (HPV) [1]. Chemotherapy, radiotherapy, surgery and immunotherapy are the methods used to treat patients with cervical cancer. However, with the help of nanomedicine and novel delivery systems, more of the efficacy of these methods can be achieved. In this paper, we aim to investigate the capacity of nanomedicine in establishing new cervical cancer treatments. As a barrier for tumor cells, the tumor micro-environment [2] provides conditions for tumor cells to continue to multiply and evade the immune mechanism [3], which is also the main reason for the poor prognosis of tumor treatment. Hypoxia, low pH, endogenous H2O2, and GSH excess are essential features of TME [4]. Here, in response to the physicochemical properties of TME, the design of TME-specific activated nanoparticles is of great significance for imaging diagnosis and precise treatment of tumors. MnO2 is a promising inorganic nanomaterial with the advantages of simple preparation, low price, and environmental friendliness [5]. In addition, MnO2 can specifically respond to excess GSH in the TME. Glutathione (GSH), which is overexpressed in tumor cells, has strong scavenging effect on free radicals. The high-priced manganese is reduced to Mn2+ by GSH [6], and the generated Mn2+ reacts with excess H2O2 in the TME to produce cytotoxic ROS [7]. In the meantime, GSH is converted to oxidized glutathione (GSSH), reducing the clearance of reactive oxygen species. Mn element has MRI imaging function, so it has an excellent biological application prospect. However, MnO2’s therapeutic effect is often limited by low reactivity and insufficient endogenous H2O2 in tumors. To overcome these limitations, temperature can be used to accelerate the Fenton [8] or Fenton-like [9] reaction rate, making the design of nanoparticles with both PTT and CDT effects promising.

The Mo element in MoS2 has a high atomic number and can provide CT imaging [10], while MoS2 has good photothermal [11] properties and can provide PTT [12] and Photothermal imaging (PTI) properties, which has good biological application prospects. The ROS produced by CDT can also inhibit the overexpression of heat shock proteins, thereby improving the PTT effect [13].

Therefore, we designed MoS2@MnO2-PEG nanoparticles that possess both PTT [14] and CDT effects and the two treatment modalities promote each other to achieve better therapeutic results [15, 16].

TME possesses higher GSH [17] content than normal tissues, making it an attractive target for cancer therapy. In this study, we developed nanoparticles and a therapeutic system, MoS2@MnO2-PEG, that specifically respond to GSH in the TME [18]. The nanoparticles were designed with MoS2 as the skeleton structure, and MnO2 was wrapped on the surface using a simple hydrothermal reaction to form a mesoporous core–shell structure [19,20,21]. Next, to improve the stability and monodispersity of MoS2@MnO2 NSs in aqueous solution and facilitate their further biomedical utilization, mPEG-NH2 was used for the surface modification of MoS2@MnO2 NSs.The two react by electrostatic bonding. This structure possesses both PTT and CDT modes, and the two modes promote each other to achieve better therapeutic results [22,23,24]. Additionally, the nanoparticles provide CT, PTI, and MRI three-modal imaging [25, 26] functions, enabling accurate and effective tumor diagnosis and treatment [27]. Compared with previous materials, the nanoparticles synthesized in this study combine two imaging modes to realize multimodal imaging of nanomaterial [28].To improve the solubility and suspension stability of the nanoparticles in water, they were modified with polyethylene glycol (mPEG-NH2) to form MoS2@MnO2-PEG (Scheme 1). The modified nanoparticles showed significant antitumor ability in vitro and in vivo, making them a promising candidate for further biomedical research.

Scheme 1
scheme 1

Schematic diagram of the preparation of MoS2@MnO2-PEG and the antitumor effect of CDT combined with PTT. a Preparation of MoS2@MnO2 and further polyethylene glycosylation reactions. b After intravenous injection of tumor-bearing mice, in vivo PTT combined with CDT treatment, including GSH depletion, Fenton-like response, and enhanced ROS production

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Experiments

Chemicals

Ethanol and ammonium hydroxide were purchased from DAMAO chemical reagent plants. Ammonium molybdate was provided by Sigma. Hydrazine hydrate, ethylene glycol, DA-HCl, KMnO4, Rhodamine B (RhB), NaN3, and Methylene blue (MB) were purchased from Shanghai Aladdin Biochemical Technology Co Ltd. 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT), Calcein-AM, PI and 2′,7′-dichlorofuorescin diacetate (DCFH-DA) were provided by Solarbio. No further purification was performed on any of the reagents.

Preparation of MoS2@MnO2-PEG

Preparation of MoS2 involved dispersing 27.5 mg of ammonium molybdate in 12.5 mL of ethylene glycol solution through ultrasonic treatment for 10 min. Next, 147 μL of hydrazine hydrate (80%) was added, and the solution was subjected to ultrasonic treatment for 40 min and transferred to a 25 mL reactor for 10 h at 140 °C. After the reaction, the material was cooled to room temperature, washed with acetone three times, centrifuged for 5 min at 8000 rpm, and the pellets were collected and dried in a vacuum oven at 80 °C for 24 h.

To prepare MoS2@MnO2, 10 mg of dried MoS2 was dispersed in 10 mL of Tris–HCl (10 mmol L−1) in water through ultrasonic treatment for 10 min until the solution was clear. Then, 1 mL of 1 mg mL−1 of DA-HCl was added and stirred for 30 min. Subsequently, 2 MnO4 was added to the solution, and the reactants were stirred for 4 h and cenmL of centrifuged. KMnO4 was used as raw material, dopamine was used as reducing agent, and MnO2 was coated on MoS2 surface by REDOX method.

The black powder obtained was washed with deionized water three times to obtain MoS2@MnO2 [29].

For the preparation of MoS2@MnO2-PEG, 5 mg of MoS2@MnO2 samples were dispersed in 10 mL of deionized water, and 2 mL of mPEG-NH2 (10 mg mL−1) was added. The solution was stirred for 24 h at room temperature, and black powder nanoparticles MoS2@MnO2-PEG were obtained.

Characterization

The morphology and structure of the materials were analyzed through transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The crystal structure of the materials was determined using X-ray diffraction (XRD). The synthesized materials were further characterized using X-ray photoelectron spectroscopy (XPS), UV–vis spectroscopy, and Fourier transform infrared (FTIR) spectroscopy.

Photothermal performance

The photothermal performance of MoS2@MnO2-PEG was evaluated based on drug concentration, power density, and photostability. To investigate its photothermal properties, the following three aspects were explored: (a) A series of concentration gradients of MoS2@MnO2-PEG were prepared and irradiated with an 808 nm laser (1.5 W cm−2). Temperature changes were monitored every 30 s for 10 min, and the temperature at 0, 1, 3, 5, 7, and 10 min were photographed and recorded with a thermal imager. Then, the subsequent processing was carried out. (b) MoS2@MnO2-PEG with a concentration of 200 μg mL−1 was exposed to lasers with power densities of 1 W cm−2, 1.5 W cm−2, and 2 W cm−2 at 808 nm. Temperature changes were monitored every 30 s for 10 min, and the data were recorded. (c) 0.5 mL of MoS2@MnO2-PEG (200 μg mL−1) was irradiated with a laser switch repeatedly for five cycles (1.5 W cm−2), and the temperature was recorded.

Chemodynamic performance

To detect the formation of ROS, methylene blue (MB) was used as an indicator. (a) The effect of GSH concentration on ROS was explored by dispersing the prepared MoS2@MnO2-PEG in acetic acid buffer at pH 5.0, adding a series of concentration gradients of GSH (0 mmol L−1, 0.5 mmol L−1, 1.0 mmol L−1), and incubating at 37 °C for 30 min. MB (10 μg mL−1) and H2O2 (100 mmol L−1) were added to the solution, and the mixture was incubated at 37 °C for 30 min. The solution was then centrifuged, and the supernatant was taken for UV–Vis absorbance. (b) Two control experiments were conducted to explore the effect of temperature on ROS: one set up at 37 °C and the other at 60 °C. The remaining experiments were performed as described above. (c)To determine the type of ROS produced, the prepared MoS2@MnO2-PEG was dispersed in acetic acid buffer at pH 5.0, and GSH (1.0 mmol L−1) was added. The mixture was incubated at 60 °C for 30 min. Phosphate buffer saline (PBS), MoS2@MnO2-PEG, Isopropyl alcohol (IPA), NaN3, and p-benzoquinone (PBQ) were added successively to capture ·OH, 1O2, and ·O2−. IPA captured ·OH, NaN3 captured 1O2, PBQ captured ·O2−. Finally, MB (10 μg mL−1) and H2O2 (100 mmol L−1) were added to the solution, and the mixture was incubated at 60 °C for 30 min.

Cell experiments

Cell uptake

HeLa cells were seeded into a cell culture dish at a density of 1 × 105 and cultured for 24 h. To evaluate the potential of MoS2@MnO2-PEG nanoparticles for cell fluorescence imaging, RhB was loaded into the nanoparticles. Next, 1.0 mL of the MoS2@MnO2-PEG nanoparticles dispersed in DMEM medium was added to each confocal dish and incubated for different time periods (0 h, 1 h, 2 h, 4 h, and 6 h). After incubation, the medium was discarded and the cells were washed twice with PBS. DAPI was then added to stain the nucleus, and the cells were incubated for 30 min before observation and photography under a confocal microscope. This protocol allowed us to assess the ability of the MoS2@MnO2-PEG nanoparticles to label cells and provide clear images of the nucleus for cell fluorescence imaging.

Detect ROS generation

HeLa cells were seeded in 6-well plates at a density of 1 × 105 and cultured overnight. After 24 h, the cells were treated with DCFH-DA (1 × 10−6 M) for 40 min. To evaluate ROS scavenging ability of MoS2@MnO2-PEG nanoparticles, three capture agents were used: PBQ (60 mM) as an ·O2− trapping agent, IPA (60 mM) as a capture agent for ·OH, and NaN3 (60 mM) as a capture agent for 1O2. Six groups of experiments were set up: (a) PBS group, (b) MoS2@MnO2-PEG group, (c) MoS2@MnO2-PEG + Laser group, (d) MoS2@MnO2-PEG + Laser + IPA group, (e) MoS2@MnO2-PEG + Laser + PBQ group, and (f) MoS2@MnO2-PEG + Laser + NaN3 group. The fluorescence intensity of DCF was measured to evaluate the ROS scavenging ability of MoS2@MnO2-PEG nanoparticles. This experimental design allowed us to investigate the effectiveness of MoS2@MnO2-PEG nanoparticles in scavenging ROS, which has important implications for their potential biomedical applications.

In vitro cytotoxicity

To evaluate the cytotoxicity of MoS2@MnO2-PEG nanoparticles, MTT assay was performed. Different conditions of MoS2@MnO2-PEG dispersed in DMEM were incubated for 12 h and 24 h. MTT (0.5 mg mL−1) was added to each well and incubated for 4 h; the medium was discarded, followed by the addition of 150 μL DMSO. The absorbance at 490 nm was measured to determine cell viability.

To assess the type of ROS that trigger apoptosis, the Calcein-AM/PI method was used. HeLa cells were seeded at a density of 1 × 105 in 6-well plates and incubated for 24 h. Five sets of experiments were conducted: (a) PBS group, (b) MoS2@MnO2-PEG group, (c) PBQ (60 mM) + MoS2@MnO2-PEG group, (d) IPA (60 mM) + MoS2@MnO2-PEG group, and (e) NaN3 (60 mM) + MoS2@MnO2-PEG group. After 4 h of incubation, DMEM was discarded and Calcein-AM/PI probes were added, followed by incubation in the dark for 30 min. The results were recorded using fluorescence microscopy. This experimental design allowed us to investigate the cytotoxicity of MoS2@MnO2-PEG nanoparticles and the type of reactive oxygen species that trigger apoptosis, which are essential for their potential biomedical applications.

Tumor model

Female Balb/c mice (ages: about 6 weeks; body weights: about 18 g) were selected as animal models to mimic HeLa cancer cells. The mice were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. and approved by the Animal Ethics and Use Committee of Shanxi Medical University (IACUC 2017–018). The study was conducted in compliance with ethical guidelines and the mice were euthanized at the end of the treatment.

In vivo biocompatibility assay

Female Balb/c mice were divided into four groups: (a) PBS; (b) PBS + Laser; (c) MoS2@MnO2-PEG, and (d) MoS2@MnO2-PEG + Laser. The mice received an intravenous injection of the drug (5 mg kg−1, 200 μL) and their body weights were measured every two days. After 14 days of treatment, the main organs of the mice were harvested and stained with hematoxylin and eosin (H&E) to assess any potential histological changes. This experimental design allowed us to investigate the potential toxicity of MoS2@MnO2-PEG nanoparticles and their safety for use in biomedical applications.

Imaging experiments

In vitro MR imaging

To investigate the relationship between the concentration of MoS2@MnO2-PEG and T1-weighted MRI signal under in vitro conditions, a series of concentration gradients were prepared for excess GSH-pretreated MoS2@MnO2-PEG in 200 μL centrifuge tubes. The MRI signals of the samples were then detected to assess the linear relationship between the concentration of MoS2@MnO2-PEG and T1-weighted MRI signal. This experimental design allowed us to evaluate the potential of MoS2@MnO2-PEG nanoparticles as contrast agents for MRI imaging.

In vivo MR imaging

To evaluate the potential of MoS2@MnO2-PEG nanoparticles as contrast agents for T1-weighted MR imaging in vivo, the nanoparticles were injected into tumor-bearing nude mice through the tumor. T1-weighted MR imaging was then performed, and the gray values of the MR signal were recorded. This experimental design allowed us to assess the ability of MoS2@MnO2-PEG nanoparticles to enhance the contrast of MR imaging in vivo, which is important for their potential biomedical applications.

Results and discussion

Characterization

The morphology of the nanoparticles was characterized by TEM, SEM, and DLS. The TEM results (Fig. 1a) demonstrated that the synthesized MoS2@MnO2 was a homogeneous spherical particle with a size of approximately 80 nm. The hydrated particle size (Fig. 1h) of the nanoparticles was measured to be 77.47 nm, consistent with the TEM results. The SEM images of MoS2 (Fig. 1b) and MoS2@MnO2 (Fig. 1c) showed the in-situ growth of MnO2 on the surface of MoS2, confirming the successful preparation of MoS2@MnO2. The potential (Fig. S1) of MoS2, MoS2@MnO2, and MoS2@MnO2-PEG was measured. The surface potential of MoS2 was − 40 mV, while the surface potential of MoS2@MnO2-PEG, formed after wrapping MnO2 on its surface by redox reaction, was − 23.2 mV. To improve its biocompatibility, the surface potential of MoS2@MnO2-PEG was modified to − 11.4 mV by electrostatic modification of mPEG-NH2 on its surface. The potential test results confirmed the successful preparation of MoS2@MnO2-PEG.

Fig. 1
figure 1

Characterization of MoS2@MnO2. a TEM images of MoS2@MnO2. b SEM images MoS2, and c MoS2@MnO2. d XPS spectra of MoS2, e XPS spectra of S 2p, f Mo 3d. g FTIR spectrum of MoS2@MnO2. h The hydrated particle size of MoS2@MnO2

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The successful synthesis of MoS2 was confirmed by XPS (Fig. 1d), which revealed peaks for Mo, S, C, and O. The two main peaks of Mo 3d5/2 and Mo 3d3/2 of MoS2 were observed at 231.67 and 228.45 eV (Fig. 1f), respectively. The high-resolution spectrum of S 2p showed the binding energy of S at 2p3/2 and S 2p1/2 at 162.6 eV and 161.8 eV, respectively (Fig. 1e). These results confirmed the successful preparation of MoS2.

The successful preparation of MoS2 and MoS2@MnO2 was further characterized by infrared spectroscopy (Fig. 1g), which showed that the peak of MoS2 was located at about 467 cm−1, corresponding to the characteristic peak of Mo–S vibration, confirming the successful preparation of MoS2. Distinct peaks of Mn–O vibrations at 550 cm−1 were observed in the infrared spectrum of MoS2@MnO2, characterizing the successful preparation of MoS2@MnO2.

The UV–Vis absorption spectroscopy (Figure S2) of MoS2@MnO2-PEG revealed that it was widely absorbed in the near-infrared I region, and the absorbance increased with drug concentration, demonstrating its potential as a photothermal agent. The photothermal properties of MoS2@MnO2-PEG were investigated by exploring the influence of concentration (Fig. 2a) and laser power (Fig. 2b) on the temperature changes of MoS2@MnO2-PEG under 808 nm laser irradiation. The temperature increased with the concentration of MoS2@MnO2-PEG, and at 200 μg mL−1, the temperature increased from 27 to 65 °C after 10 min of 1.5 W cm−2 laser irradiation, achieving the purpose of photothermal treatment of tumors. Therefore, 200 μg mL−1 MoS2@MnO2-PEG was used for subsequent experiments. The temperature changes of MoS2@MnO2-PEG were positively correlated with the laser power (1 W cm−2, 1.5 W cm−2, and 2 W cm−2), and after 1.5 W cm−2 laser irradiation, the temperature of the solution increased from 27 to 65 °C, achieving the purpose of PTT treatment of tumors. Thus, a laser with 1.5 W cm−2 power was used as the experimental power in subsequent experiments.

Fig. 2
figure 2

a Temperature change curves of different concentrations of MoS2@MnO2-PEG under 808 nm laser irradiation. b Temperature change curves of MoS2@MnO2-PEG dispersion (200 μg mL−1) at different laser power densities. c temperature plot of MDMP dispersion irradiated by an 808 nm laser for five on–off cycles. d Infrared thermal imaging pictures of different concentrations of MoS2@MnO2-PEG at different irradiation times. e Investigate the effect of GSH concentration on ROS content produced by MoS2@MnO2-PEG. f The influence of temperature on the ROS content

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The NIR thermal imager was used to record the temperature of different concentrations of MoS2@MnO2-PEG (0 μg mL−1, 100 μg mL−1, 150 μg mL−1, and 200 μg mL−1) at different times (0 min, 1 min, 3 min, 5 min, 7 min, 10 min) under 1.5 W cm−2 808 nm laser irradiation (Fig. 2d). The photothermal properties of the material gradually increased with the increase in material concentration, and the photothermal properties increased with the laser irradiation time.

The study investigated the photostability and photothermal stability of MoS2@MnO2-PEG. The results showed that the absorbance of MoS2@MnO2-PEG did not change significantly before and after laser irradiation (Figure S3), indicating excellent photostability. Moreover, the temperature response curve of MoS2@MnO2-PEG remained unchanged after five cycles of laser heating and cooling (Fig. 2c), demonstrating its exceptional photothermal cycle stability. Moreover, according to Roper’s method, the photothermal conversion efficiency (η) of MoS2@MnO2-PEG (200 μg mL−1) was calculated to be around 27.1% (Figure S4), demonstrating its excellent light-to-heat conversion capability [30]. These findings suggested that the synthesized MoS2@MnO2-PEG nanocomposite possesses superior photostability and photothermal stability properties that are relevant for various biomedical and industrial applications.

Chemodynamic performance

In this study, we evaluated the chemodynamic performance of MoS2@MnO2-PEG nanoparticles in the tumor microenvironment (TME). The MnO2 coating on the outer layer of the nanoparticles facilitated the reaction with excess GSH in the TME to produce Mn2+. Further, Mn2+ decomposed H2O2, ultimately generating cytotoxic ROS34. Using MB as a ROS probe, we investigated the effect of GSH concentration on ROS content produced by MoS2@MnO2-PEG (Fig. 2e). Gradual decrease in absorbance of MB at 660 nm with increasing GSH concentration indicated a corresponding increase in ROS content generated by the MoS2@MnO2-PEG system, thus verifying its chemodynamic performance. In order to confirm the synergistic enhancement phenomenon of photothermal therapy and chemodynamic therapy,35,36 we explored the influence of temperature on the ROS content (Fig. 2f), which showed that the absorbance value of MB at 660 nm was significantly lower at 60 °C than at 37 °C, indicating that the system produced more active oxygen species.

To investigate the types of ROS produced by the nanoparticles, we used PBQ as a trapping agent for O2−, IPA as a capture agent for ·OH, and NaN3 as a trapping agent for 1O2. Our findings suggested that MoS2@MnO2-PEG nanoparticles primarily produce ·OH instead of O2−,1O2 (Figure S5), as shown by the increased absorbance value of MB at 660 nm in the MoS2@MnO2-PEG + IPA treatment group but no significant difference in the absorbance value of MB at 660 nm in the MoS2@MnO2-PEG + NaN3 group compared to the MoS2@MnO2-PEG + PBQ group. These findings highlighted the potential of MoS2@MnO2-PEG nanoparticles as an effective chemodynamic therapy agent for cancer treatment.

Cellular experiments

Cell uptake

To investigate the cellular uptake of MoS2@MnO2-PEG nanoparticles and evaluate their ability to generate ROS at the cellular level, we conducted a series of experiments. First, we used rhodamine B to label the surface of MoS2@MnO2-PEG nanoparticles and observed their uptake by HeLa cells using laser confocal microscopy (Fig. 3d). The intracellular fluorescence increased with the extension of the incubation time, indicating that the uptake of MoS2@MnO2-PEG by cells gradually increased. 3.4.2.ROS generation.

Fig. 3
figure 3

a Calcein-AM/PI dual staining for identifying the live or dead cells. b The ability of MoS2@MnO2-PEG to generate ROS at the cellular level. c HeLa cells viability after incubation with different groups. d Cellular uptake of MoS2@MnO2-PEG observed by CLSM for different periods

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ROS generation

Next, we evaluated the ability of MoS2@MnO2-PEG to generate ROS at the cellular level using the DCFH-DA probe (Fig. 3b). Compared with the PBS group, fluorescence was detectable in the cells of the MoS2@MnO2-PEG group, indicating that ROS was generated in the system. Moreover, the fluorescence intensity of the system after laser irradiation was stronger in the MoS2@MnO2-PEG + Laser group than in the MoS2@MnO2-PEG group, indicating that the system had a PTT-enhanced CDT effect. The types of ROS produced by MoS2@MnO2-PEG were also examined using different ROS trap detection systems. The fluorescence of the MoS2@MnO2-PEG + PBQ group and the MoS2@MnO2-PEG + NaN3 group was strong, while the fluorescence of the MoS2@MnO2-PEG + IPA group almost disappeared, indicating that the type of reactive oxygen species produced by MoS2@MnO2-PEG was ·OH.

In vitro cytotoxicity

We then assessed the cytotoxicity of MoS2@MnO2-PEG using normal human cells (HcerEpic Cell) and HeLa cells (Fig. S6). MoS2@MnO2-PEG at 400 μg mL−1 was incubated with normal human cells for 12 h or 24 h, and the survival rate of cells was more than 80%, indicating that MoS2@MnO2-PEG had good biological safety and was non-toxic to normal cells. However, the survival rate of 200 μg mL−1 MoS2@MnO2-PEG-treated HeLa cells was reduced to 60% after only 12 h incubation due to the release of Mn2+ in response to excessive GSH in the tumor microenvironment.

To evaluate the phototoxicity of MoS2@MnO2-PEG to tumor cells (Fig. 3c), we conducted experiments using VC + MoS2@MnO2-PEG-PEG and VC + MoS2@MnO2-PEG + Laser groups. The survival rate of VC + MoS2@MnO2-PEG-PEG group cells was above 80%, indicating that the cells were protected from CDT because VC had the effect of clearing ROS. However, the cell survival rate of VC + MoS2@MnO2-PEG + Laser group was about 50%, indicating that MoS2@MnO2-PEG had PTT properties. Moreover, the survival rate of cells in the MoS2@MnO2-PEG + Laser group was about 20%, indicating that PTT/CDT synergistic therapy had a better effect on tumor cell killing.

Finally, we visually assessed the cell-killing properties of MoS2@MnO2-PEG using Calcein-AM/PI staining. The experimental results demonstrated (Fig. 3a) that the cells of the control groups, PBS and PBS + Laser, exhibited robust viability and the laser illumination alone did not induce cell death. The addition of VC in the VC + MoS2@MnO2-PEG group conferred protection against CDT through effective scavenging of ROS. Notably, the presence of MoS2@MnO2-PEG induced partial cell death, indicating the effectiveness of CDT. Furthermore, the introduction of laser irradiation to the VC + MoS2@MnO2-PEG group confirmed the potent PTT capabilities of MoS2@MnO2-PEG, with pronounced cell death observed. Most notably, the PTT/CDT combination therapy had a significantly enhanced tumor-killing effect, as evidenced by considerable cell death observed in the VC + MoS2@MnO2-PEG + Laser group. Additionally, the type of free radicals generated was identified as primarily ·OH using a trapping agent (Fig. S7).

Imaging experiments

MR imaging

Previous studies have demonstrated that the Mn element possesses T1 imaging capabilities, which have been effectively imparted to MoS2@MnO2-PEG for MRI applications. In order to evaluate the potential of MoS2@MnO2-PEG as an NMR agent, in vitro nuclear magnetic imaging was conducted, with varying concentrations of nanoparticles subjected to pretreatment with excess GSH and incubation for 0.5 h. The resulting T1 NMR signal was observed to increase in accordance with material concentration (Fig. 4a). Subsequently, MoS2@MnO2-PEG was administered via tumor injection in tumor-bearing nude mice, and in vivo T1 imaging was performed. The resulting T1 signal at the tumor site was significantly different from other sites, indicating the excellent T1 MRI ability of MoS2@MnO2-PEG.

Fig. 4
figure 4

a T1-weighted MR images with multiple concentrations and intratumoral T1-weighted MR images of MoS2@MnO2-PEG. b CT images with various concentrations and intratumoral CT images of MoS2@MnO2-PEG. c Thermal imaging images of different groups

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CT imaging

The high atomic number of Mo and its ability to decay X-rays make it an effective CT imaging agent. This study aimed to evaluate the potential of MoS2@MnO2-PEG as a CT contrast agent through in vitro and in vivo CT imaging. A range of MoS2@MnO2-PEG concentrations were prepared to assess its in vitro CT imaging effect, and it was observed that the brightness increased in accordance with increasing MoS2@MnO2-PEG concentration, confirming its good CT imaging ability. In comparison with the tumor site prior to the injection of composite materials, the CT signal at the tumor site after MoS2@MnO2-PEG injection was enhanced, indicating its good in vivo CT imaging ability (Fig. 4b).

Photothermal imaging

The photothermal imaging capabilities of MoS2@MnO2-PEG were investigated in vivo by injecting it into tumor-bearing nude mice, followed by irradiation of the tumor site with an 808 nm laser (1.5 W cm−2) for 10 min (Fig. 4c). The temperature of the tumor site in the experimental group increased by 25 °C, while little change was observed in the control group, indicating the excellent photothermal imaging ability of MoS2@MnO2-PEG.

Antitumor effect in vivo

In order to assess the antitumor effect in vivo, HeLa cells were inoculated to establish a nude mouse model, with the tumor volume increasing to approximately 100 mm3. The mice were divided into four groups: PBS group, PBS + Laser group, MoS2@MnO2-PEG group, and MoS2@MnO2-PEG + Laser group, with intratumoral injection and laser irradiation (1.5 W cm−2) at 808 nm for 10 min administered in the latter two groups (Fig. 5a, b, d). During the 14-day treatment period, the tumors in the MoS2@MnO2-PEG group exhibited a smaller size due to the CDT effect, measuring approximately 400 mm3. The tumors in the MoS2@MnO2-PEG plus laser group were eliminated.

Fig. 5
figure 5

a Tumor changes during 14 days of PBS, PBS + Laser, MoS2@MnO2-PEG, and MoS2@MnO2-PEG + Laser treatment. b tumor volume, c body weight, and d tumor weight after the treatment of PBS, PBS + Laser, MoS2@MnO2-PEG, and MoS2@MnO2-PEG + Laser

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Following treatment, the nude mice were euthanized, and their main organs and tumor tissues were collected for analysis. The weight of the mice in all four groups increased slightly during the treatment period (Fig. 5c), and no deaths occurred, indicating the good biocompatibility of MoS2@MnO2-PEG. Liver and renal function in the experimental group showed no significant difference compared to the control group (Fig. S8). Pathological sections were analyzed to assess the effects of MoS2@MnO2-PEG on the heart, liver, spleen, lungs, and kidneys of nude mice, and no apparent abnormalities were observed in any of the four groups (Fig. 6), indicating the excellent biological safety of MoS2@MnO2-PEG.

Fig. 6
figure 6

H&E staining images of main organs (heart, liver, spleen, lungs, and kidneys) of HeLa tumor-bearing mice in the groups of PBS, PBS + Laser, MoS2@MnO2-PEG, and MoS2@MnO2-PEG + Laser

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Conclusion

This study presented a diagnostic and therapeutic integrated nanosystem, MoS2@MnO2-PEG, which demonstrated excellent performance in PTI, MRI and CT multimodal imaging, and PTT/CDT synergistic therapeutic effects. In vitro tests confirmed the successful preparation of the material and its favorable PTT and CDT properties. MoS2@MnO2-PEG exhibited high cellular uptake rates, lower toxicity to normal cells, and strong tumor cell-killing ability in cell uptake experiments, demonstrating its excellent antitumor performance. Furthermore, our results from PTI, MRI, and CT imaging confirmed the ability of MoS2@MnO2-PEG for multimodal imaging. Animal experiments established the biological safety and excellent therapeutic effects of MoS2@MnO2-PEG on tumor-bearing nude mice. Our approach integrating CDT/PTT synergies through MoS2@MnO2-PEG held great significance in promoting the integration of tumor diagnosis and treatment and provided a new strategy for tumor treatment.