A dual chemical-photothermal drug delivery platform inhibits LPS-induced oxidative damage by suppressing the p38 MAPK pathway in cardiomyocytes

Xi Han; Yue Li; Xuelian Zhu; Pengxia Zhang

doi:10.25259/AJC_348_2025

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Original Article

2025

:18;

3482025

doi:

10.25259/AJC_348_2025

A dual chemical-photothermal drug delivery platform inhibits LPS-induced oxidative damage by suppressing the p38 MAPK pathway in cardiomyocytes

Xi Han^a,, Yue Li^a,, Xuelian Zhu^b,*, Pengxia Zhang^a,*

aKey Laboratory of Microecology-immune Regulatory Network and Related Diseases School of Basic Medicine, Jiamusi University, Jiamusi, Heilongjiang, China

bDepartment of Anesthesiology, First Affiliated Hospital of Jiamusi University, Jiamusi, Heilongjiang, China

*Corresponding authors: E-mail addresses: zhuxuelian@jmsu.edu.cn (X. Zhu); jmsdxzpx@163.com (P. Zhang)

Received: 2025-04-06, Accepted: 2025-05-24, Epub ahead of print: 2025-08-04, Published: 2025-08-23

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Abstract

Heart failure (HF) is a complex clinical syndrome marked by impaired cardiac function, often driven by cardiomyocyte apoptosis. The latter is induced by myocardial infarction, atherosclerosis, or ischemia-reperfusion injury, with oxidative stress playing a central role in progression. In this study, a therapeutic molecule (compound I) targeting HF was synthesized and loaded into a zwitterionic amphiphilic polymer nanocarrier system (PSBMA-CP1@I), constructed via coordination between compound I and CP1. The structural and optical properties of PSBMA-CP1@I were systematically characterized. Fluorescence spectroscopy revealed that the introduction of compound I led to significant emission quenching of the PSBMA-CP1 scaffold under 365 nm excitation (from ∼432 nm), indicating successful drug loading. Fluorescence titration experiments conducted in the 0–2400 pM range showed a concentration-dependent response with a Stern–Volmer quenching constant (K_SV) of 1.63 × 10⁶ M⁻¹ and good linearity in the low concentration region (0–750 pM, R² = 0.9930), demonstrating high detection sensitivity. pH-responsive release tests indicated enhanced release of compound I under acidic conditions (pH 5.0), with a cumulative release of up to 75% within 60 minutes, compared to a much slower release at pH 7.4. Moreover, in vitro studies in lipopolysaccharide (LPS)-stimulated H9C2 cells showed that PSBMA-CP1@I effectively attenuates oxidative damage and modulates p38-MAPK signaling, supporting its application in anti-inflammatory and cardioprotective therapies.

Keywords

Cardiomyocyte

Chemical-photothermal

Oxidative damage

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1. Introduction

Heart failure (HF) is a clinical syndrome resulting from structural and functional cardiac impairments that compromise ventricular ejection or filling capacity [1,2]. The consequent reduction in myocardial contractility leads to inadequate cardiac output, systemic hypoperfusion, and congestion, marking HF as the terminal stage of various cardiovascular disorders [3,4]. Oxidative stress and apoptosis are central pathological features of HF progression [5,6]. Specifically, oxidative stress, defined by an imbalance between reactive oxygen species (ROS) and antioxidant defenses, drives cardiomyocyte injury and death through excessive ROS accumulation [7-9]. This exacerbates pathological remodeling, impairs cardiac function, and increases the risk of arrythmia [10-12]. Furthermore, P38 mitogen activated protein kinase (MAPK) activation in cardiomyocytes promotes fibrosis by inducing pro-inflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, underscoring its role in HF-related oxidative injury [13-15]. Based on this rationale, compound I was primarily designed and synthesized as an angiotensin-converting enzyme (ACE) inhibitor. Free small-molecule chemotherapeutic agents currently employed in clinical practice still face multiple challenges, encompassing poor tumor-targeting specificity, rapid systemic clearance, unavoidable cytotoxicity, and inadequate tumor penetration. Moreover, cytoreductive procedures were frequently correlated with technical complexity and wound healing risks. Hence, the development of novel therapeutic strategies for peritoneal metastatic cancer emerged as a major research focus.

Metal organic frameworks (MOFs) are crystalline porous materials created by ligand bonding between organic ligands and inorganic metal ions [16-18]. The functional and structural diversity brought by variable ligands and metal ions endows MOFs with tunable architectures, properties, and broad application potential [19-21]. Owing to their superior physicochemical characteristics, such as adjustable pore sizes and high surface areas, MOFs demonstrated exceptional suitability as drug carriers, enabling enhanced drug loading capacity, stability, and therapeutic efficacy through controlled release mechanisms [22-24]. Generally, hydrogen bonding, π-π stacking, van der Waals forces, chemical bonding, or electrostatic interactions were employed to combine with drug solutions through pore encapsulation, covalent conjugation, or surface adsorption to load drugs into MOFs [25,26]. Certain MOFs demonstrated inherent antibacterial activity via organic/natural antibacterial ligands or antimicrobial metal ions, offering perfect platforms for further antibacterial agent immobilization to provide synergistic effects and enhanced medication stability [27-29]. For instance, vancomycin-loaded Ag-MOFs encapsulated within nanoplatelet vesicles formed a composite material demonstrating pH-responsive drug release, with in vivo anti-infective efficacy significantly surpassing that of free vancomycin. However, most MOFs existed in powder form and showed difficult recovery [30,31]. To streamline retrieval processes and enhance carrier stability, diverse framework substrates were incorporated during fabrication to support MOF structures.

With the rapid advancement of nanotechnology, diverse composite materials integrating MOFs with other nanocarriers have been developed for drug delivery. For example, Cao’s group synthesized porous porphyrin-based MOF nanoparticles (PCN-224) using meso-tetra (4-carboxyphenyl) porphyrin (H₂TCPP) as organic linkers and Zr(IV)-oxo clusters as nodes, achieving tebuconazole loading and controlled release [32]. This system demonstrated dual photodynamic therapy (PDT) and bactericidal activities against Alternaria alternata, Pseudomonas syringae pv, tomato, as well as Xanthomonas campestris. In another study, Slawin’s team designed a bio-MOF with a mono-dispersed chitosan-coated layer (CS/Bio-MOF) as a target-selective and pH-responsive platform for the delivery of doxorubicin in breast cancer therapy [33]. These therapeutic nanoagents effectively mitigated challenges associated with free chemotherapeutics, including rapid clearance and suboptimal tumor targeting specificity, while concurrently reducing MOF-related toxicity.

To construct an efficacious drug delivery system with controlled drug release and high drug loading capacity, we synthesized compound I, followed by CP1. CP1 was then loaded into a Poly(sulfobetaine methacrylate) (PSBMA) amphiphilic polymer nanoparticle carrier, prepared via free-radical polymerization utilizing [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfonopropyl)ammonium (SBMA) and N, N’-bis(acryloyl)cysteamine (BAC) as the monomer and as the crosslinking agent with S-S bonds, respectively. Lastly, compound I was conjugated with the PSBMA polymer to create the drug-loaded polymer-based nanomotor PSBMA-CP1@I (Scheme 1). We systematically examined the structure, morphology, release ability, and drug loading of the PSBMA-CP1@I composite, as well as the impact of its photothermal properties on drug release. Additionally, we assessed the inhibitory effects of the composite material on lipopolysaccharide (LPS)-induced oxidative damage in cardiomyocytes and further explored its regulatory effect on the p38 MAPK signaling pathway.

2. Materials and Methods

2.1. Chemicals and characterization

All the reagents were at least analytical grade, available on demand, and didn’t need further purification. fourier transform infrared spectroscopy (FTIR) spectra were obtained fron a Nicolet iS50 FTIR spectrometer (Thermo Fisher, USA) with KBr pellets, and attenuated total reflection (ATR). X-ray diffraction (XRD) was conducted using a D8 Advance diffractometer system (Bruker, Germany), with Ni-filtered Cu Kα radiation (λ = 0.154 nm). A cold field emission scanning electron microscope (SEM) (JEOL, JSM-7800F, Japan) was used for capturing SEM images.

2.2. The preparation and characterization of compound I and CP1

Compound I: The compound was synthesized with 3-fluorobenzaldehyde (150 mg, 1 equiv.), malononitrile (105 mg, 1.2 equiv.), and 4-hydroxy-6-methyl-2-pyrone (200 mg, 1 equiv.) as starting materials through a Knoevenagel condensation. The reaction was conducted in anhydrous ethanol or dichloromethane (20 mL) at 60°C with potassium carbonate (2 mg, 1/10 equiv.) as the catalyst. Upon completion of the reaction, the mixture was cleaned in water, extracted by dichloromethane, and subsequently purified by silica gel column chromatography (EA:PE = 1:10) to give the pure target compound.

CP1: A mixture formed by 0.10 mmol HCOOH, 8 mL DI water, 0.12 mmol AgNO₃, as well as 0.30 mmol N, N-diphenylpyridin-4-amine ligand was sealed in a 15 mL stainless steel vessel lined with Teflon and reacted for 2 days at 85°C. The autoclave was cooled to RT over 18 h, yielding colorless crystals with a 42.1% yield (based on the N, N-diphenylpyridin-4-amine ligand). Elemental analysis for C₁₈H₁₃AgN₂O₂: N=7.05%; H=3.30%; C=54.43%. Found: N=7.04%; H=3.24%; C=54.40%. Table 1 presents single-crystal data.

Table 1. Crystallographic data for CP1 and compound I.

Designation of the sample	CP1	Compound I
Empirical formula	C₁₈H₁₃AgN₂O₂	C₁₆H₁₁FN₂O₃
Formula mass	397.17	298.27
Crystal system	Monoclinic	Monoclinic
Space group	P2₁/n	P2₁/n
Temperature/K	293(2)	293(2)
a [Å]	10.6223(2)	10.875(4)
b [Å]	9.8506(2)	8.586(3)
c [Å]	14.7070(2)	15.468(5)
α [°]	90	90
β [°]	93.3480(10)	99.791(4)
γ [°]	90	90
V [Å³]	1536.26(5)	1423.3(8)
Z	4	4
D_calcd.[mg·m^-3]	1.717	1.392
μ [mm^-1]	10.618	0.107
F [000]	792	744
θ [°]	5-73.735	2.13-25.00
Reflections collected	5604 / 3003	8844
Goodness-of-fit on F²	1.040	0.958
Final R indices [I>2σ(I)]	R₁ = 0.0609, wR₂ = 0.1665	R₁ = 0.0530, wR₂ = 0.1653
CCDC	2446348	2446349

2.3. The synthesis of PSBMA-CP1@I

Firstly, 5 mg of compound I, 10 mg of CP1, and 30 mg of PSBMA were dissolved in water (10 mL) and sonicated for 30 min. The mixture was subsequently stirred at RT for 4 h. Upon completion of the reaction, the mixture was centrifuged at 15,000 rpm for 5 min, and the product was cleaned in water to remove unbound CP1 and compound I. The final product was named PSBMA-CP1@I. The supernatant was gathered, and the concentration of compound I and CP1 was measured with a UV spectrophotometer. The loading efficiency was computed with the Eqs. (1) and (2) below:

(1)

D r u g l o a d i n g c a p a c i t y (D L %) = (\frac{w e i g h t o f d r u g i n p a r t i c l e s}{w e i g h t o f p a r t i c l e s}) \times 100 %

(2)

E n c a p s u l a t i o n e f f i c i e n c y (E E %) = (\frac{w e i g h t o f d r u g i n p a r t i c l e s}{w e i g h t o f f e e d d r u g}) \times 100 %

2.4. Determination of malondialdehyde (MDA) and superoxide dismutase, (SOD) levels

Rat cardiomyocyte H9C2 (ATCC, USA) was seeded in dulbecco’s modified eagle medium (DMEM) (VivaCell Biosciences, China) containing 10% fetal bovine serum (FBS) (VivaCell Biosciences, China). Cells in lipopolysaccharide (LPS) group were treated with 1 μg/mL LPS for 24 h. Cells in the drug-treated group were treated with PSBMA-CP1@I on top of treatment with LPS for 24 h. The levels of superoxide dismutase (SOD) and malionaldehyde (MDA) were assayed by SOD and MDA assay kits (Nanjing Jianjian Bioengineering Institute, China) in accordance with the manufacturer’s instructions.

2.5. Western blot

H9C2 cells (ATCC, Manassas, USA) were subjected to lysis, and the isolated protein underwent electrophoresis. Proteins were transferred to polyvinylidene fluoride (PVDF) (Millipore, Billerica, USA) membranes and inoculated overnight at 4°C with the primary antibody. The membrane was subsequently incubated with the secondary antibody conjugated to horseradish peroxidase (HRP) (Beyotime, Shanghai, China). Visualization of the bands was accomplished using an ECL kit (Beyotime, Shanghai, China). The primary antibodies employed in this study were as follows: gasdermin D antibody (#97558, CST, USA), p38 MAPK antibody (#9212, CST, USA), and phospho-p38 MAPK antibody (#9211, CST, USA).

3. Results and Discussion

3.1. Structure description of CP1

Single crystal XRD (SCXRD) analysis suggests that CP1 crystallized in the P21/n space group in monoclinic crystal systems, and possessed a 2D layer framework. Its asymmetric unit was made up of an HCOO^- anion, a flexible N-donor organic ligand, and an Ag ion. As shown in Figure 1, the center Ag(I) ion adopted the five-connect coordination model with one N, two C, and two O atoms. The N and C atoms came from three different organic ligands. The two O atoms were from the HCOO^- anion.

The coordination setting of the Ag(I) in CP1. The symmetry code: #1: 1.5+x, 1.5-y, -0.5+z; #2: 1+x, y, -1+z.

In CP1, the C and N atoms from the flexible ligand coordinate singly to Ag(I) due to the rotational properties of the organic ligands, which give a 2D zigzag layer structure (Figure 2a). Further, the adjacent layers were connected by van der Waals forces to generate a 3D dense packing structure (Figure 2b). Topological analysis reveals that the center Ag(I) with organic ligands can be regarded as 3-linked nodes, thereby CP1’s entire framework can be reduced as a node-free 3-linked hcb topological net with a (6³) point symbol (Figure 2c). To further validate the coordination behavior of the Ag⁺ ions and their synergistic framework-forming ability with organic ligands, we conducted a detailed comparison between the constructed CP1 and previously reported Ag-based complexes in the literature [34,35].

(a) 2D layer structure in CP1; (b) The CP1’s 3D dense packing structure; (c) The hcb topological net of CP1.

3.2. Structure description of compound I

The SCXRD data of compound I revealed that it is in a monoclinic crystal system with P21/n. The molecular structure comprises a benzene ring C: C11-C16 and two 6-membered rings (ring A: O2 and C4-C8; ring B: O1 and C4-C8), as illustrated in Figure 3. Atom C7 of ring A is linked by a methyl group (-C9H₃); atom C8 of ring A is linked to an O3 atom via a C=O bond. Atoms C8 of ring A are attached to an O3 atom through a C=O bond. Rings A and B are attached to each other by a C4-C5 bond. The C1 and C2 atom of ring B is attached to an amino group (-N2H₂) and a nitrile group (-C10N1), respectively. The C3 atom of ring B is linked to ring C through the C11 atom. The C13 atom of ring C is attached to a fluorine atom. In addition, adjacent molecules of compound I are further bonded via van der Waals forces and intermolecular H-bonds (N1-H2A.....N2: 2.2458 Å, O3-H2B.....N2: 2.0886 Å) (Figure 4a) to form a 3D dense stacked structure (Figure 4b).

(a) H-bonds between the neighboring molecules; (b) Compound I’s dense packing molecule structure.

3.3. Characterization of PSBMA-CP1@I

In accordance with single-crystal characterization of compound I and CP1, as shown in Figure 5(a), the structure of PSBMA-CP1@I was analyzed by FTIR, with the FTIR spectra of PSBMA (black curve), PSBMA-CP1 (red curve), and PSBMA-CP1@I (blue curve). The PSBMA spectrum shows characteristic absorption peaks at approximately 1100 and 1640 cm⁻¹, corresponding to C-O-C and C=O stretching vibrations. When CP1 is added, a new peak at 1510 cm⁻¹ appears in the red curve, indicating an interaction between PSBMA and CP1. The blue curve of PSBMA-CP1@I shows further peak shifts and the appearance of new peaks, confirming that compound I was successfully encapsulated in the PSBMA matrix. As shown in Figure 5(b), SEM imaging revealed that the PSBMA-CP1@I composites exhibited aggregated yet distinguishable nanostructures with irregular block-like morphologies. The particles appear to have a rough surface texture and display an average dimension of approximately 500 nm. This nanoscale architecture is conducive to cellular uptake and favorable for achieving efficient drug delivery. Figure 5(c) shows that the ζ potential measurement of PSBMA-CP1@I indicates a surface charge of approximately +35 mV, suggesting good suspension stability and the ability to prevent aggregation through electrostatic repulsion. Dynamic light scattering (DLS) analysis (Figure 5d) shows that the hydrodynamic diameter of PSBMA-CP1@I peaks at around 500 nm, with particles primarily concentrated in the 300-600 nm range, is suitable for drug delivery. The thermogravimetric analysis (TGA) curve of PSBMA-CP1@I (Figure 5e) shows significant weight loss at approximately 200°C, with a total weight loss of about 30% at 500°C. This weight loss was related to the thermal degradation of organic components in the composite, confirming its thermal stability. Additionally, Figure 5(f) shows the nitrogen adsorption/desorption isotherms of CP1, PSBMA, and PSBMA-CP1. The Brunauer-Emmett-Teller (BET) method calculated the specific surface area of PSBMA to be about 20 m²/g, PSBMA-CP1 to be 35 m²/g, and PSBMA-CP1@I to be 45 m²/g, indicating that the composite material had a higher surface area due to the successful encapsulation of CP1, enhancing its drug loading and release potential. The isotherms also exhibit typical type IV behavior, suggesting that the composite material has a mesoporous structure, further confirming its porous nature. In summary, the characterization results confirmed that PSBMA-CP1@I composite material possessed advantageous physicochemical properties, including successful encapsulation, excellent thermal stability, suitable particle size, stable surface charge, and enhanced specific surface area, all of which give it great promise for drug release and loading.

Characterization of PSBMA-CP1@I composite. (a) FTIR spectra. (b) SEM image. (c) Zeta potential distribution. (d) DLS analysis. (e) TGA curve. (f) Nitrogen adsorption/desorption and BET surface area. (g) PXRD analysis of PSBMA-CP1@I.

To comprehensively validate the phase purity and structural stability of the PSBMA-CP1@I composite material, powder XRD (PXRD) analysis was performed. As shown in Figure 5(g), the experimentally obtained PXRD pattern (red curve) was in excellent agreement with the simulated PXRD pattern based on the single-crystal structure (black curve), with no obvious impurity peaks observed. This result indicated that the material possessed good crystallinity and high phase purity, and its structure remained stable throughout the synthesis and functional modification processes.

3.4. Photothermal performance study

To address the dual challenges of targeted delivery and controlled drug release in the treatment of HF, photothermal-responsive nanomaterials emerged as a highly promising strategy. These materials can convert near-infrared (NIR) light into localized heat, enabling spatiotemporally controlled drug release at lesion sites while minimizing systemic toxicity to healthy tissues. In this study, the photothermal performance of the PSBMA-CP1@I nanoplatform was systematically evaluated. The experimental results demonstrated that its pronounced photothermal effect primarily originates from the π-conjugated coordination polymer CP1, which exhibits strong NIR absorption and efficient non-radiative relaxation pathways. Under 808 nm laser irradiation, PSBMA-CP1@I dispersions at a concentration of 2 mg/mL showed a significant temperature rise, in contrast to negligible heating observed in the pure water control group (Figure 6a). The temperature increase was positively correlated with nanoparticle concentration, laser power, and irradiation duration (Figure 6b).

Figure 6.

(a) Temperature change of PSBMA-CP1@I dispersion (1 mL) under 1.8 W/cm² laser irradiation. (b) Temperature profile of PSBMA-CP1@I (2.0 mg/mL, 1 mL) under varying power irradiation. (c) Photothermal stability of PSBMA-CP1@I (2.0 mg/mL, 1 mL) under an irradiation of 2.0 W/cm².

The photothermal conversion mechanism is mainly attributed to π–π* transitions within the conjugated polymer backbone and enhanced electron delocalization facilitated by the metal–ligand coordination framework, resulting in rapid and efficient thermal energy generation. Meanwhile, the PSBMA coating improves water dispersibility and colloidal stability, ensuring uniform heat distribution during irradiation. Notably, the nanoplatform maintained a consistent thermal response over multiple on/off laser cycles, indicating excellent photothermal stability (Figure 6c). Such localized heat generation plays a vital role in HF therapy by enabling drug release in response to pathological conditions such as ischemia or inflammation, thereby enhancing the precision and timeliness of treatment.

3.5. Fluorescence testing and drug release

To comprehensively assess the performance of PSBMA-CP1 as a drug delivery vehicle, its drug-loading capacity, fluorescence response characteristics, and pH-sensitive release behavior were systematically investigated. As shown in Figure 7(a), PSBMA-CP1 exhibited a prominent fluorescence emission peak at approximately 432 nm under 365 nm excitation. Upon loading with compound I, the resulting complex (PSBMA-CP1@I) displayed nearly complete fluorescence quenching, indicating that the introduction of compound I induces significant quenching, which can serve as an effective indicator for drug loading and release monitoring.

(a) Fluorescence spectra of PSBMA-CP1 before and after drug loading; (b) Fluorescence titration with compound I; (c) Stern–Volmer plot; (d) pH-dependent drug release profiles.

To evaluate the quenching efficiency and detection sensitivity of the system toward compound I, fluorescence titration was conducted across a concentration range of 0–2400 pM. As presented in Figure 7(b), a progressive decrease in fluorescence intensity was observed with increasing concentrations of compound I, demonstrating a clear concentration-dependent quenching behavior. The Stern–Volmer plot (Figure 7c) revealed a nonlinear upward trend, suggesting the involvement of both static and dynamic quenching mechanisms. Within the low-concentration region (0–750 pM), a strong linear relationship (R² = 0.9930) was observed in the inset, and the corresponding Stern–Volmer constant (K_SV) was calculated to be 1.63 × 10⁶ M⁻¹, indicating high sensitivity in the picomolar range.

Furthermore, the pH-dependent release behavior of PSBMA-CP1@I was evaluated under varying pH conditions (5.0, 6.0, and 7.4). In an acidic environment (pH 5.0), the release rate of compound I was significantly accelerated, reaching a cumulative release of 75% within 60 minutes, whereas release was notably slower under neutral conditions (Figure 7d). This pH-responsive behavior is particularly relevant in pathological conditions such as HF, where the local tissue microenvironment becomes mildly acidic (pH 6.0–6.9) due to ischemia, hypoxia, and inflammation. These results demonstrate that PSBMA-CP1 exhibits excellent drug-loading efficiency, fluorescence responsiveness, and pH-triggered release performance, highlighting its potential as a smart delivery platform for targeted therapeutic applications in complex disease microenvironments.

3.6. PSBMA-CP1@I inhibit LPS induced damage to H9C2 by suppressing the p38 MAPK pathway

Following treatment of H9C2 cells with LPS, a significant decrease in SOD content and an increase in MDA content were detected. However, when LPS-treated H9C2 cells were loaded with PSBMA-CP1@I, a contrasting response was observed, with a decrease in MDA levels (Figure 8a) and an increase in SOD levels (Figure 8b). These findings suggest that PSBMA-CP1@I has the potential to attenuate LPS-induced damage to H9C2 cells. Since the p38 MAPK signaling pathway exerts an essential role in a variety of pathological and physiological processes like inflammation, cellular cycle and stress, growth, and apoptosis, we examined whether PSBMA-CP1@I had a role in modulating the p38 MAPK pathway. After LPS treatment of H9C2 cells, the level of p-p38 MAPK was significantly increased (Figure 8c), indicating that the p38 MAPK signaling pathway was activated. However, upon treatment with PSBMA-CP1@I, the phosphorylation level of p38 MAPK was reduced, suggesting that p-p38 MAPK pathway activation was suppressed.

(a) The effect of PSBMA-CP1@I on MDA in H9C2 cells. (b) The impact of PSBMA-CP1@I on SOD in H9C2 cells. (c) The effect of PSBMA-CP1@I on p38 MAPK pathway. **, *** and **** indicates P<0.01, 0.001 and 0.0001, respectively.

4. Conclusions

In summary, compound I was synthesized for HF treatment, coordinated with CP1, and successfully encapsulated in a zwitterionic polymer-based nanocarrier (PSBMA-CP1@I). Structural and optical analyses confirmed efficient drug loading, with fluorescence quenching behavior yielding a Stern–Volmer quenching constant (K_SV) of 1.63 × 10⁶ M⁻², indicating high sensitivity at picomolar levels. The system demonstrated pH-responsive release behavior, with cumulative release reaching 75% under acidic conditions (pH 5.0), mimicking the HF microenvironment. PSBMA-CP1@I also exhibited favorable photothermal performance, with temperature elevation dependent on irradiation time and power. In vitro studies revealed that the system alleviated oxidative stress and modulated p38-MAPK signaling in LPS-stimulated H9C2 cells. These findings underscore the potential of PSBMA-CP1@I as a multifunctional therapeutic platform for precise and responsive HF treatment.

Acknowledgment

This study was supported by the Research project of Jiamusi University (S2013-038), the Research project of Education Department of Heilongjiang Province (2016-KYYWF-0600), the Research project of Education Department of Heilongjiang Province (2020-KYYWF-0291), and Joint Guidance Project of the Natural Science Foundation of Heilongjiang, China (JJ2022LH1061).

CRediT authorship contribution statement

Xi Han and Yue Li are in charge of the chemistry part of the experiment; Xuelian Zhu is in charge of the biology part of the experiment; Pengxia Zhang wrote the paper.

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

For supporting data from the outcomes of this study, contact the corresponding author.

Use of Generative artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of AI-assisted technology for assisting in the writing of the manuscript and no images were manipulated using AI.

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A dual chemical-photothermal drug delivery platform inhibits LPS-induced oxidative damage by suppressing the p38 MAPK pathway in cardiomyocytes

Abstract

Keywords

Cardiomyocyte

Chemical-photothermal

Oxidative damage

1. Introduction

2. Materials and Methods

2.1. Chemicals and characterization

2.2. The preparation and characterization of compound I and CP1

2.3. The synthesis of PSBMA-CP1@I

2.4. Determination of malondialdehyde (MDA) and superoxide dismutase, (SOD) levels

2.5. Western blot

3. Results and Discussion

3.1. Structure description of CP1

3.2. Structure description of compound I

3.3. Characterization of PSBMA-CP1@I

3.4. Photothermal performance study

3.5. Fluorescence testing and drug release

3.6. PSBMA-CP1@I inhibit LPS induced damage to H9C2 by suppressing the p38 MAPK pathway

4. Conclusions

Acknowledgment

CRediT authorship contribution statement

Declaration of competing interest

Data availability

Use of Generative artificial intelligence (AI)-assisted technology for manuscript preparation

References

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