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A multifunctional nanoplatform for dexamethasone delivery and dual-mode colorimetric/fluorescent sulfide ion detection to alleviate juvenile sepsis
*Corresponding author: E-mail address: hqwz20250815@163.com (Q. Hu)
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Received: ,
Accepted: ,
Abstract
Juvenile sepsis is a fatal hyperinflammatory syndrome marked by excessive cytokine release, for instance IL-6 and TNF-α, causing multiple organ failure. Although dexamethasone (Dex) is a potent anti-inflammatory drug, its juvenile application is limited by low bioavailability and systemic side effects. Hydrogen sulfide (H₂S), derived from sulfide ions (S2⁻), plays a dual role in inflammation, making its dynamic monitoring clinically valuable. Here, we constructed a multifunctional theranostic nanoplatform—OAP–ATPMS–1@CP1@Dex—which combines octenyl succinic anhydride–modified polysaccharide (OAP) with a dysprosium-based coordination polymer (CP1) exhibiting peroxidase-like activity and fluorescence at 450 nm. In the presence of H₂O₂, CP1 catalyzes TMB oxidation to oxTMB, inducing a fluorescence inner filter effect; S2⁻ inhibits this reaction, enabling sensitive dual-mode S2⁻ detection as an indirect H₂S indicator. The nanosystem accumulates at inflammatory sites via the EPR effect, enabling controlled Dex release to suppress cytokine overproduction while minimizing toxicity. This platform integrates targeted anti-inflammatory therapy with real-time inflammatory signal sensing, offering a precise treatment strategy for juvenile sepsis.
Keywords
Dexamethasone
Dual-mode
Juvenile sepsis
1. Introduction
Sepsis, a systemic hyperinflammatory syndrome triggered by infection, exhibits high morbidity and mortality among juveniles, whose immature immune systems render them particularly vulnerable to uncontrolled inflammatory cascades [1,2]. This pathological process leads to excessive release of pro-inflammatory cytokines such as IL-8, IL-6, and TNF-α, often progressing to multiple organ dysfunction or even septic shock, severely endangering their growth and survival [3]. Thus, the dual demand for effective suppression of hyperinflammation and precise monitoring of inflammatory dynamics remains a critical unmet clinical need to improve outcomes in juvenile sepsis [4].
In anti-inflammatory therapy, dexamethasone, a classic glucocorticoid, alleviates systemic inflammation by inhibiting proinflammatory cytokine synthesis and blocking signaling pathways, and has been adopted as an adjuvant treatment for sepsis [5]. However, its clinical utility in juveniles is hampered by limitations of conventional administration, including low bioavailability, widespread systemic distribution, and potential endocrine disturbances [6]. These disadvantages highlight how urgent it is to create tailored medication delivery methods that maximize therapeutic effectiveness and reduce off-target effects [7].
Effective sepsis management, however, extends beyond optimized drug delivery—it necessitates real-time tracking of inflammatory progression, which relies on accurate monitoring of key signaling molecules. Hydrogen sulfide (H₂S), a pivotal gaseous mediator, exhibits concentration-dependent roles in inflammation: low levels exert antioxidant and anti-inflammatory effects through inhibiting the NF-κB pathway, whereas high levels may promote inflammation and cellular damage [8]. Notably, dynamic fluctuations in H₂S levels correlate closely with sepsis severity and prognosis [9]. Thus, real-time monitoring of H₂S (and its derivative S2⁻) not only elucidates inflammatory mechanisms but also provides a basis for therapeutic evaluation, complementing anti-inflammatory strategies [10].
Dual-mode colorimetric/fluorescent sensing has emerged as a promising tool for such monitoring, as its dual-channel analysis mitigates environmental interference [11]. However, existing platforms often require cascaded detection of multiple materials and struggle to achieve compatibility under identical experimental conditions [12,13]. Concurrently, because of their stability, large surface areas, and tunable porosity, MOFs—porous crystalline materials consisted of organic ligands and metal centers—have demonstrated promise in drug delivery, while their peroxidase-like activity and fluorescence properties enable sensing applications [14-17]. Nevertheless, most studies focus on single functions (e.g., drug loading or sensing), failing to address the integrated demand for “therapy plus monitoring”—a critical gap in current research [18,19].
To bridge this gap, we designed a multifunctional system leveraging two key materials: octenyl succinic anhydride-modified polysaccharide (OAP) and a dysprosium (Dy)-based MOF (designated CP1). OAP, an amphiphilic polysaccharide derivative, offers broad drug compatibility (both hydrophilic and lipophilic), inherent biocompatibility, and biodegradability [20]. Functionalization with 3-aminopropyltrimethoxysilane (ATPMS) enhances mechanical stability and provides abundant sites for further modification, facilitating integration of sensing modules. CP1, synthesized via a one-pot solvothermal method, simultaneously serves as a drug carrier and a sensing unit, exhibiting a characteristic fluorescence emission at 453 nm and possesses potent peroxidase-like activity [21,22]. Their synergistic integration forms the basis of our theranostic platform [23,24].
The resulting system, OAP-ATPMS-1@CP1@dexamethasone, was constructed by encapsulating CP1 (loaded with dexamethasone) within OAP-ATPMS modified with a synthetic small molecule (1), ensuring biocompatibility and detection performance. Its sensing mechanism relies on the following: colorless 3,3’,5,5’-TMB is oxidized by CP1 to blue oxidized TMB (oxTMB) in the presence of H₂O₂. This creates a fluorescence inner filter effect (IFE) with the carrier, allowing for dual-mode detection. Upon introduction of S2⁻, redox reactions between H₂O₂ and S2⁻ impair CP1’s enzymatic activity, reducing oxTMB production, decreasing UV absorbance at 652 nm, and restoring fluorescence. This property enables sensitive intracellular S2⁻ detection, indirectly reflecting H₂S levels. As a nanoparticulate system, it accumulates at inflammatory sites through the enhanced permeability and retention (EPR) effect, enabling localized, controlled release of dexamethasone to enhance anti-inflammatory efficacy while reducing systemic toxicity. In summary, this study integrates H₂O₂-responsive dexamethasone delivery with real-time S2⁻/H₂S monitoring, addressing both “imprecise anti-inflammation” and “delayed monitoring” in juvenile sepsis. By evaluating its regulatory effects on inflammatory cytokines and sensing performance, we aim to provide experimental evidence for optimizing precision therapy in juvenile sepsis.
2. Materials and Methods
2.1. Materials and characterization
Unless otherwise noted, all chemical solvents and reagents were of analytical quality and utilized without further purification. The UV–vis spectra were obtained with a a U-4100 spectrophotometer (Hitachi, Japan) and UV-2450 spectrophotometer (Shimadzu, Suzhou). Fluorescence measurements were performed on an F-7000 fluorescence spectrophotometer (Hitachi, Japan). Utilizing a field-emission scanning electron microscopy (FE-SEM) (Hitachi S-4800, Japan) at 20 kV, the morphology of materials was investigated. On a TD-3500 diffractometer (Dandong, China) with nickel-filtered Cu Kα radiation (λ = 0.15406 nm), X-ray diffraction (XRD) patterns were recorded. Fourier transform infrared (FT-IR) spectra were acquired via a Nicolet iS5 spectrometer (Thermo Fisher, USA). The porosity and specific surface area were determined through the Brunauer-Emmett-Teller (BET) method with N₂ adsorption–desorption isotherms acquired on an ASAP 2020 system (Micromeritics, USA). For identifying ROS, electron paramagnetic resonance (EPR) spectroscopy was implemented on a Bruker EMXplus-6/1 spectrometer (Bruker, Germany), with DMPO utilized as the spin-trapping agent for O₂•⁻ and •OH radicals.
2.2. Synthesis of OAP-ATPMS-1@CP1@dexamethasone
OAP (300 mg) was oxidized by reacting with NaIO₄ (64 mg, 0.30 mmol) at 0–4°C for 2 h, followed by termination with ethylene glycol (0.2 mL, 3.6 mmol). After concentration and washing with deionized water, OAP-CHO (approx. 260 mg) was obtained. Pre-acid-treated compound 1 (80 mg, ∼0.25 mmol) and OAP-CHO (150 mg) were coupled in a CH₃CN/DMF system under DCC/DMAP catalysis for 12 h. After removal of by-products, concentration, and washing, OAP-1 (approx. 180 mg, yield 72%) was obtained. Subsequently, OAP-1 (150 mg) was reacted with ATPMS (100 μL, 0.60 mmol) in MeOH in the presence of AcOH for 6 h, followed by aging for 12 h. Precipitation, concentration, and washing afforded OAP-ATPMS-1 (approx. 170 mg, yield 78%, Scheme S1). CP1 (20 mg) was dispersed in EtOH/H₂O (1:1, 20 mL) and sonicated for 10 min before mixing with OAP-ATPMS-1 (40 mg) and adjusting the pH to 7.2–7.4. The mixture was stirred at RT for 24 h, centrifuged, and washed to yield OAP-ATPMS-1@CP1 (approx. 50 mg). Finally, OAP-ATPMS-1@CP1 (50 mg) was incubated with dexamethasone (10 mg, in EtOH, 1 mg∙mL⁻1) at 25°C under light-protected shaking for 12 h. The product was centrifuged, washed, and collected to obtain OAP-ATPMS-1@CP1@Dexamethasone (55 mg).
2.3. Establishment of inflammatory model
The macrophage cell line (RAW264.7) was provided by the American Type Culture Collection (ATCC, Manassas, VA, USA). Cells were cultivated in DMEM medium (Gibco, Thermo Fisher Scientific, Waltham, MA, USA) with 100 μg∙mL-1 streptomycin (Sigma-Aldrich, St. Louis, MO, USA), 100 U∙mL-1 penicillin, as well as 10% FBS (HyClone, Logan, UT, USA). The culture was maintained at 37°C with 5% CO₂ in a humidified incubator (Thermo Fisher Scientific, Waltham, MA, USA). Logarithmic phase RAW264.7 cells were inoculated into 96-well plates (Corning, Corning, NY, USA) at a density of 5×10⁴ cells per well. Each well received 100 μL of media. To enable adhesion, cells were cultivated for 24 h under the previously specified circumstances. To elicit an inflammatory response, lipopolysaccharide (LPS) (Escherichia coli O111:B4, Sigma-Aldrich, St. Louis, MO, USA) was administered to all groups except the blank control group. LPS was added at a concentration of 1 μg∙mL-1, with 100 μL of medium containing the corresponding concentration of LPS added to each well, and the culture was continued for 6 h to establish a sepsis-related inflammatory model.
2.4. Nanoparticle intervention experiment
For the nanoparticle intervention experiment, the cells were separated into five groups: the LPS model group, the blank control group, and the empty nanoparticle control group (which had the same concentration of nanoparticles as the drug-loaded group), the free dexamethasone control group (1 μM), and OAP–ATPMS–1@CP1@dexamethasone group (1 μM). Specifically, after 6 h of LPS induction, the empty nanoparticle control group was added with nanoparticle solution at the corresponding concentration, the free dexamethasone control group was supplemented with 1 μM free dexamethasone, and the OAP–ATPMS–1@CP1@dexamethasone group was treated with 1 μM OAP–ATPMS–1@CP1@dexamethasone, followed by continuous incubation for another 24 h to complete the intervention process.
2.5. ELISA detection
Cell culture supernatants from each experimental group were collected, centrifuged for 10 min at 3000 × g at 4°C, and the supernatants were reserved for future use. The instructions of ELISA kits (Cusabio, China) were meticulously followed in order to identify the levels of IL-8, IL-6, and TNF-α in the supernatants.
3. Results and Discussion
3.1. Characterization of OAP-ATPMS-1@CP1@dexamethasone
The structures of CP1 and compound 1 were characterized by SCXRD, and Table S1 and Figures S1-S2 display their schematic representations. The crystalline structures of the prepared materials were first investigated by XRD (Figure 1a). Strong crystallinity of CP1 was demonstrated by its distinct and crisp diffraction peaks. Upon coating with OAP–ATPMS–1, the resulting OAP–ATPMS–1@CP1 displayed broader and less intense peaks, suggesting a partial loss of crystallinity due to the silica-based shell formation. After dexamethasone loading, the diffraction peaks further decreased in intensity, indicating increased amorphization, which may benefit drug loading and release by providing more accessible diffusion pathways. Surface functional groups were characterized using FT-IR spectroscopy (Figure 1b). In OAP–ATPMS–1@CP1, characteristic bands of Si–O–Si (1082 cm⁻1), Si–C (814 cm⁻1), and CP1’s ligand framework (1504–1657 cm⁻1) were clearly observed. After drug loading, additional absorption bands corresponding to dexamethasone appeared, including –OH and C=O stretching at 3401 cm⁻1 and 1732 cm⁻1, confirming that the drug has been successfully incorporated into the composite matrix. The porous properties of OAP-ATPMS-1@CP1@dexamethasone were further examined by N₂ adsorption–desorption isotherms (Figure 1c). The isothermal profiles presented type IV characteristics accompanied by H3-type hysteresis loops, suggesting the presence of a mesoporous structure. A total pore volume of 0.215 cm3∙g⁻1 and a high surface area of 112.46 m2∙g⁻1 were found by BET analysis. The corresponding pore size distribution curve (Figure 1d) showed a narrow peak centered at 3.5 nm, confirming the uniform mesoporous nature of the material. The clearly defined mesopores and large surface area are advantageous for effective drug loading and prolonged release, while also facilitating molecular diffusion during therapeutic application. The morphology and structural integrity of the OAP–ATPMS–1@CP1@dexamethasone composite were further examined by SEM and PXRD analyses. As shown in Figure S3(a), the PXRD patterns of the composite before and after exposure to physiological (pH 7.4) and mildly acidic (pH 6.5) conditions for 24 h displayed nearly identical diffraction features, confirming its excellent crystallinity and chemical stability under biological environments. The SEM image (Figure S3b) reveals irregularly aggregated flake- and rod-like particles with rough surfaces and distinct layered textures, indicative of a porous and hierarchically assembled structure. Such morphology is consistent with the CP1-based framework and is expected to facilitate drug encapsulation and diffusion within the nanosystem. These results collectively demonstrate that the composite maintains high structural stability and morphological robustness, supporting its potential for sustained drug delivery applications.
- (a) XRD patterns, (b) FT-IR spectra, (c) N₂ adsorption–desorption isotherms, and (d) pore size distribution curves of OAP–ATPMS–1@CP1@dexamethasone.
The electrochemical performance of materials was examined with EIS and CV. As shown in Figure S4(a), both OAP–ATPMS–1@CP1 and OAP–ATPMS–1@CP1@Dexamethasone exhibited well-defined redox peaks, indicating efficient electron transfer capability. The dexamethasone-loaded composite displayed higher redox peak currents compared to the unloaded sample, suggesting enhanced electrochemical activity and improved charge transport, possibly due to the drug’s contribution to the overall conductivity. The EIS Nyquist plots (Figure S4b) reveal that in the high-frequency range, OAP–ATPMS–1@CP1@Dexamethasone exhibits a smaller semicircle diameter than OAP–ATPMS–1@CP1, which is indicative of a reduced charge-transfer resistance (Rct) and better electron transfer efficiency. This enhanced conductivity is favorable for potential biosensing and electrochemical drug release applications.
3.2. Catalytic performance and mechanism
Given the critical role of oxidative stress and reactive oxygen species (ROS) in regulating inflammatory cascades during sepsis, we further investigated the peroxidase-like catalytic performance of OAP–ATPMS–1@CP1@Dexamethasone in the TMB/H₂O₂ system and elucidated its ROS generation mechanism, aiming to clarify its potential in modulating the septic inflammatory microenvironment. In order to assess the peroxidase-like activity of the nanocomposite, 3,3′,5,5′-TMB was employed as the chromogenic substrate. As shown in Figure 2(a), TMB alone displayed negligible absorbance in the visible region, and only weak oxidation occurred in the presence of H₂O₂. In contrast, the OAP–ATPMS–1@CP1@Dexamethasone/H₂O₂/TMB system exhibited two prominent absorption peaks at 652 and 370 nm, with the latter corresponding to the characteristic oxidized TMB (oxTMB) signal, accompanied by a distinct color change, from colorless to blue, indicating strong peroxidase-like activity of the nanoplatform. The steady-state kinetic analysis for TMB oxidation (Figure 2b) revealed a typical Michaelis–Menten behavior, with the initial reaction velocity increasing rapidly at low TMB concentrations and reaching saturation at higher concentrations. The Michaelis–Menten fitting gave a Km value of 0.099 mM and a Vmax of 8.22 × 10⁻⁸ M∙s⁻1, suggesting high substrate affinity and catalytic efficiency. The catalytic mechanism was further investigated using ROS scavenging experiments (Figure 2c). The addition of thiourea (TH, •OH scavenger) and p-benzoquinone (p-BQ, O₂•⁻ scavenger) significantly reduced the catalytic activity, while NaN₃ (1O₂ scavenger) showed a negligible effect, suggesting that O₂•⁻ and •OH are the primary active species in the catalytic process. This conclusion was confirmed by electron paramagnetic resonance (EPR) spectra (Figure 2d), which displayed the characteristic DMPO–•OH and DMPO–O₂•⁻ adduct signals.
- (a-d) Catalytic activity and ROS mechanism analysis of OAP–ATPMS–1@CP1@Dexamethasone in the TMB/H₂O₂ system; (a) UV–vis absorption spectra of various reaction systems; (b) Effect of TMB concentration on reaction rate; (c) Effect of different ROS scavengers on catalytic activity; (d) EPR spectra of DMPO–O₂•⁻ and DMPO–•OH.
The influences of temperature, pH, reaction duration, and catalyst concentration were assessed in order to maximize the catalytic performance (Figure S5). The peroxidase-like activity peaked at pH 3.5 (Figure S5a) and 30°C (Figure S5b), with prolonged reaction time leading to a steady increase in activity until 20 min, after which it plateaued (Figure S5c). Activity increased dramatically when the catalyst concentration was raised from 5 to 20 mg∙L⁻1, followed by a gradual increase up to 50 mg∙L⁻1 (Figure S5d). Therefore, pH 3.5, 30°C, 20 min reaction duration, and 20 mg∙L⁻1 catalyst concentration were found to be the optimal catalytic conditions.
Based on the stability evaluation (Figure S6a–S6d), OAP–ATPMS–1@CP1@Dexamethasone exhibited remarkable durability under various conditions. As shown in Figure S6(a), after 6 weeks of storage at room temperature, the nanozyme retained over 90% of its initial catalytic activity, demonstrating excellent long-term stability. Similarly, all five independent synthesis batches maintained above 95% relative activity (Figure S6b), confirming high reproducibility and batch-to-batch consistency of the preparation process. pH tolerance tests revealed that the nanozyme retained nearly full activity in the acidic range (pH 2–5), with the highest value observed around pH 3–4, while activity gradually declined under neutral-to-alkaline conditions, dropping to ∼70% at pH 12 (Figure S6c). Temperature stability tests showed that activity remained above 95% across a broad range (20–60°C), with a slight optimum around 30–40°C, and still maintained 90% activity at 70°C (Figure S6d). These results indicate that OAP–ATPMS–1@CP1@Dexamethasone possesses excellent storage stability, reproducibility, and resilience against pH and temperature variations, making it suitable for catalytic applications under diverse physiological and pathological conditions.
3.3. Fluorescence properties of OAP–ATPMS–1@CP1@Dexamethasone
The fluorescence behavior of OAP–ATPMS–1@CP1@Dexamethasone and its applicability for fluorescence sensing within the TMB/H₂O₂ catalytic system were further investigated. As shown in Figure 3(a), under 380 nm excitation, OAP–ATPMS–1@CP1@Dexamethasone exhibited strong dual-emission peaks, with the most prominent centered at 450 nm. Upon reaction with TMB and H₂O₂ for 20 min, the fluorescence intensity was markedly quenched, whereas TMB alone showed negligible emission, indicating that the oxidized TMB (oxTMB) generated in the catalytic process significantly inhibits the fluorescence of the nanocomposite. As presented in Figure 3(b), this phenomenon may be explained by spectrum overlap between the emission of fluorophore and the UV–vis absorption of oxTMB, indicating the involvement of the IFE. To clarify the quenching mechanism, fluorescence lifetime measurements were performed (Figure 3c), revealing lifetimes of 17.36 ns for OAP–ATPMS–1@CP1@Dexamethasone and 17.20 ns after TMB/H₂O₂ treatment. The negligible change confirms that fluorescence attenuation arises predominantly from IFE rather than dynamic quenching. This intrinsic optical modulation enables the integration of fluorescence sensing into the TMB-based colorimetric detection platform, providing a dual-mode readout for ROS-related catalytic processes.
- Fluorescence quenching mechanism of OAP–ATPMS–1@CP1@Dexamethasone in the TMB/H₂O₂ system: (a) fluorescence spectra, (b) spectral overlap indicating IFE, and (c) fluorescence lifetime analysis.
3.4. Colorimetric and fluorescent dual-mode detection of S2
In view of the pivotal role of H2S in sepsis detection and treatment, different concentrations of S2⁻ were introduced into the OAP-ATPMS-1@CP1@Dexamethasone/TMB/H₂O₂ system under optimized conditions. The absorbance peak at A₆₅₂ steadily declined with rising S2⁻ concentration, according to the results (Figure 4a), showing a strong linear connection with the concentration of S2⁻ in the 0–100 μM range (R2 = 0.9985, LOD = 0.43 μM) (Figure 4b). The IFE effect was diminished in the fluorescence mode as the concentration of S2⁻ rose, leading to a notable augmentation of the emission peak intensity (Figure 4c), with a linear relationship shown in the range of 0–80 μM (R2 = 0.9985, LOD = 0.078 μM) (Figure 4d). To assess the selectivity and anti-interference capability of the sensing platform, various potential interfering species—including common inorganic ions and humic acid (HA, 1 mM)—were introduced into the detection system. As shown in Figures S7(a and b), all tested species except sulfide (S2⁻) induced negligible changes in both the absorbance and fluorescence intensity, indicating that the system exhibits excellent selectivity. Furthermore, additional analytes such as cysteine (Cys), cyanide (CN⁻), bisulfite (HSO₃⁻), ascorbic acid (AA), and glucose (Glu) were examined to further validate the platform’s specificity. The minimal signal fluctuations observed confirm that the CS-1-based sensing platform maintains high accuracy and stability even in complex environments. In line with the activity study background, S2⁻, as a derivative of H₂S, is closely associated with the dynamic changes of inflammatory signaling molecules. Under high-inflammatory conditions such as sepsis, fluctuations in H₂S concentration can directly affect the release of inflammatory cytokines for instance IL-6 and TNF-α and NF-κB signaling. Therefore, this system not only demonstrates high efficiency, stability, and selectivity for H₂S detection but also provides a powerful tool for real-time, highly sensitive monitoring of disease-related gaseous signaling molecules, with dual potential applications in both environmental monitoring and biomedical diagnostics. Compared with previously reported sensing platforms for hydrogen sulfide or sulfide ions, the nanocomposite developed in this study exhibits comparable or even lower detection limits, faster response kinetics, and superior biocompatibility, underscoring its excellent sensing performance and practical application potential (Table S2). To further validate the reliability and analytical performance of the proposed sensing system, the detection results obtained using the OAP–ATPMS–1@CP1@Dex platform were compared with those from the conventional analytical technique of high-performance liquid chromatography (HPLC) (Table S3). The comparable recovery rates and precision values confirm that the accuracy and reproducibility of this nanoplatform are on par with or superior to those of the established methods, further corroborating the reliability and practical applicability of the developed system.
- Dual-mode detection of S2⁻ using the OAP-ATPMS-1@CP1@Dexamethasone/TMB/H₂O₂ system: (a) UV–vis spectra with varying S2⁻ concentrations; (b) corresponding linear calibration curve (colorimetric mode); (c) fluorescence spectra with varying S2⁻ concentrations; (d) corresponding linear calibration curve (fluorescence mode). (The blue line represents the ultraviolet absorption curve, corresponding to the left axis; the yellow line denotes the fluorescence emission spectrum, corresponding to the right axis. The colors of the lines and the Y-axis are correlated)
3.5. Cell viability assay
IL-8, IL-6, and TNF levels in the LPS model group were considerably higher than those in the blank control group, according to the detection results of inflammatory factors (Figure 5). This suggests that the LPS-induced inflammatory model was successfully established. IL-8, IL-6, and TNF levels in the empty nanoparticle control group did not differ much from those in the LPS model group, suggesting that the nanoparticle carrier itself had no obvious effect on the inflammatory response. The levels of the three inflammatory factors were somewhat lower in the free dexamethasone control group than in the LPS model group, indicating that free dexamethasone had a certain inhibitory effect on the inflammatory response. Notably, IL-8, IL-6, and TNF levels were significantly lower in the OAP–ATPMS–1@CP1@dexamethasone group than in the free dexamethasone control group, demonstrating that the OAP–ATPMS–1@CP1@dexamethasone had a stronger ability to inhibit the secretion of inflammatory factors, and their anti-inflammatory effect was superior to that of free dexamethasone.
- Effects of dexamethasone-loaded nanoparticles on production of inflammatory factors (TNF, IL-6, IL-8) *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001.
4. Conclusions
In this work, a multifunctional theranostic nanoplatform, OAP–ATPMS–1@CP1@Dex, was developed by integrating the biocompatibility and modifiability of OAP with the peroxidase-like activity and characteristic fluorescence at 453 nm of a dysprosium-based CP1, enabling synergistic drug delivery and signal detection. When H2O₂ is present, CP1 catalyzes the conversion of TMB to oxTMB, which results in an IFE fluorescence; the introduction of S2⁻ inhibits this process, resulting in decreased absorbance at 652 nm and fluorescence recovery, thus enabling highly sensitive dual-mode detection for reliable H₂S monitoring. Activity evaluation demonstrated that the platform accumulates at inflammatory sites via the EPR effect and enables controlled release of dexamethasone, significantly reducing LPS-induced pro-inflammatory cytokines, with superior anti-inflammatory efficacy compared to free dexamethasone, while the unloaded platform exhibited no significant inhibitory effect, confirming the synergistic action of the drug and carrier. This system maintains stable and sensitive S2⁻/H₂S detection even in complex matrices while achieving precise localized anti-inflammatory therapy, highlighting its dual potential for environmental monitoring and biomedical applications.
Acknowledgment
The research was supported by the Key Laboratory of Clinical Cohort Research on Bone and Joint Degenerative Diseases of Guangxi.
CRediT authorship contribution statement
Dongming Li and Yueyan Huang designed experimental scheme; Yanni Feng and Xiaoxiao Huang did experiments; Lihua Wu wrote the paper; Jingwang Huang and Qiang Hu provided experimental funding.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Data availability
Upon request, the corresponding author will provide the data that supported the conclusions of the study.
Declaration of generative AI and AI-assisted technologies in the writing process
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript and no images were manipulated using AI.
Supplementary data
Supplementary material to this article can be found online at https://dx.doi.org/10.25259/AJC_1023_2025.
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