Ultrasound assisted preparation of lignin-chitosan capped gold nanoparticles: Its evaluation for suzuki coupling and treatment of cervical cancer

Yun Xu; Ling Gao; Demei Xin; Yi Guo; Mengjiao Xu; Shu Shan

doi:10.25259/AJC_110_2025

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Original Article

2025

:18;

1102025

doi:

10.25259/AJC_110_2025

Ultrasound assisted preparation of lignin-chitosan capped gold nanoparticles: Its evaluation for suzuki coupling and treatment of cervical cancer

Yun Xu^a, Ling Gao^b, Demei Xin^c,, Yi Guo^d, Mengjiao Xu^e, Shu Shan^e,*

aDepartment of Ultrasound Diagnosis, Electric Power Teaching Hospital, Capital Medical University, No.1, Taipingqiao Xili Jia, Fengtai District, Beijing, 100073, China

bCollege of Health, Binzhou Polytechnical College, No.919, Yellow River 12th Road, Binzhou, 256603, China

cDepartment of Gynecology and Obstetrics, ChuiYangLiu Hospital Affiliated to Tsinghua University, No.2, South Muiyangliu Street, Chaoyang District, Beijing, 100024, China

dDepartment of Obstetrics and Gynecology, Shanghai East Hospital, Tongji University School of Medicine, No.150, Jimo Road, Shanghai, 200123, China

eDepartment of Obstetrics and Gynecology, Tongji Hospital, Tongji University School of Medicine, No.389, Xincun Road, Shanghai, 200065, China

*Corresponding author: E-mail address: kaixin060387@163.com (S. Shan)

Received: 2025-02-03, Accepted: 2025-06-19, Epub ahead of print: 2025-08-30, Published: 2025-09-20

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This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

Abstract

As a natural capping, reducing, and stabilizing template, lignin-chitosan (Lig-CS) hydrogel polymers were created by hydrogen bonding and cross-linking with glutaraldehyde to immobilize gold (Au) nanoparticles (Lig-CS/Au NPs) upon exposure to ultrasonic radiation. The Lig-CS/Au NPs nanocomposite’s formation was verified using a number of methods, including X-ray diffraction (XRD), Energy Dispersive X-ray (EDX)-elemental mapping, Transmission Electron Microscopy (TEM), Inductively Coupled Plasma (ICP), UV-vis, and Field-Emission Scanning Electron Microscopes (FE-SEM). The particles were found to be round, monodispersed, and roughly 7.15 nm in size by TEM imaging. Lig-CS/Au NPs are pure crystalline, as indicated by the corresponding XRD pattern. Furthermore, the Lig-CS/Au NPs’ catalytic actions were used to create biphenyl derivatives using Suzuki-Miyaura coupling. The resultant nanocatalyst showed reusability for more than seven runs without experiencing a discernible drop in activity. The cytotoxicity and anti-cervical cancer activity of Lig-CS/Au NPs against the HeLa, SiHa, and CCI-PI 19 cell lines were evaluated using the MTT test kit to evaluate their biological impact. Accordingly, the corresponding IC₅₀ values were 454, 642, and 745 µg/mL. The cell viability decreased in a dose-dependent manner during treatment with the bio-nanomaterial. Lig-CS/Au NPs’ antioxidant activity was assessed using a DPPH test, which yielded an IC₅₀ value of 72 µg/mL.

Keywords

Anti-cervical cancer

Chitosan

Gold nanoparticles

Lignin

Suzuki–miyaura

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1. Introduction

Today, nanotechnology combined with ultrasonics, effectively integrating nanoscience with biological sciences, has emerged as an interesting research area for nanomaterial synthesis and medical applications in recent years [1-5]. Numerous diagnostic methods, medication administration, therapeutic applications, and cancer treatments all rely heavily on nanoscience [6-9]. Because of their potential uses as sensors [10-12], medications [13-15], and catalysts [16,17], it is essential to synthesize gold nanoparticles (Au NPs) in a variety of sizes and forms and stabilize their colloidal suspensions. Au NPs also display notable optoelectronic effects [18], making them promising optical probes because their color changes with variations in shape and size. Furthermore, Au NPs have significant potential for various biological applications.

The distinctive qualities of chitosan, a linear polysaccharide, include antibacterial activity, biocompatibility, non-toxicity, and biodegradability. These qualities have led to the widespread use of chitosan in cosmetics, medicine, and pharmaceuticals [19-21]. Nevertheless, a significant drawback of chitosan-based polymers prevents them from being used in tissue engineering applications. Chitosan tends to inflate considerably in liquid environments, which changes its surface shape, impairs cell adherence and proliferation on its surface, and causes noticeable deterioration in its mechanical qualities [22,23]. Several scholars have suggested the addition of lignin to chitosan to address this problem. One of the most prevalent natural polymers, along with cellulose and proteins, lignin has attracted a lot of attention from scientists, especially in biomedicine [24-26]. Nearly every known oxygen-containing organic functional group is present in lignin, and these groups are essential to its reactivity [27]. According to research, lignin has exceptional sorption properties that allow it to bind a variety of bacteria, heavy metals, radioactive isotopes, and internal and external poisons. It is used to create a variety of composite materials as a filler and an active agent. According to recent studies, lignin’s antioxidant properties make it perfect for creating packaging films from thermoplastic polymers [28,29].

In organic synthesis, cross-coupling reactions are essential for creating C-C bonds [30-33]. Among various organic procedures, Suzuki coupling is an efficient method for the synthesis of biphenyl derivatives through C–C bond formation [34]. Suzuki coupling typically requires homogeneous conditions, including a palladium catalyst and a phosphine ligand, offering high reactivity and good selectivity [35]. However, challenges such as expensive reagents, long reaction times, and high temperatures remain significant barriers to their use in industrial applications.

In this work, we report the creation of a biodegradable polymeric composite (Lig-CS) based on lignin and chitosan that functions as a natural capping agent, decreasing with stabilizing template to manufacture embedded Au NPs for the first time under ultrasonic waves. Several analytical methods were used to ascertain the properties of the resultant Lig-CS/Au NP nanocomposite, which was then assessed as a heterogenous catalyst in Suzuki coupling (Scheme 1). The Lig-CS/Au NPs’ potential as a novel anticancer agent was also investigated, with a focus on preventing the proliferation of human cervical cancer cells. Its antioxidant capability, which is thought to be connected to its anticancer effects, was also investigated.

Ultrasound production of Lig-CS/Au NPs and its performance in the Suzuki coupling reaction.

2. Materials and Methods

2.1. Material and methods

The organic ingredients were acquired from Merck and used exactly as supplied. These materials included lignin (2000 kDa), chitosan (≥98% deacetylated, 50K), HAuCl₄, K₂CO₃, phenylboronic acid, and aryl halides. The cell line, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 3-(4,5-di methyl thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were obtained from Wako Pure Chemical Industries, Ltd (Japan). A TESCAN MIRA3 microscope and an energy dispersive X-ray (EDX) analyzer were used for field emission-scanning electron microscopy (FE-SEM) analysis. Transmission electron microscope (TEM) imaging was carried out using a 200 kV Philips CM10 microscope. Co Kα radiation (wavelength = 1.78897 Å) was used for X-ray diffraction (XRD) measurements, which covered a diffraction angle range of 2θ = 5° to 80°, with a power setting of 40 keV and 40 mA. Section 3.1 reports the crystallite size, which was determined using the Scherrer equation. Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES 730-ES, Varian) was used to quantitatively assess the amount of gold (Au) present in the Lig-CS/Au NPs nanocomposite. Magnetic resonance spectra of the hydrogen and carbon nuclei were acquired using the Brucker Avance spectrometer. Nuclear magnetic resonance (¹H NMR) at 400 MHz was used to study hydrogen nuclei, and ¹³C NMR at 100 MHz was used to analyze carbon nuclei. At 540 nm, cell survival was measured using the enzyme-linked immunosorbent assay (ELISA) reader model BK-EL 10A.

2.2. Lig-CS/Au NPs nanocomposite synthesis

According to the earlier report [36], 0.05 g of chitosan and 0.02 g of lignin were added to 100 mL of 1% acetic acid to create a homogenous mixture. For 12 h at 25°C, the solution was agitated to create a pure Lig-CS composite. To aid in cross-linking, a 2 mL aqueous solution of glutaraldehyde (25 w%) was then added while stirring for 12 h more after the reaction temperature had been increased to 70°C. After that, 20 mL of 1 M NaOH was added, and the mixture was agitated for 20 min at 25°C. After centrifuging the resultant Lig-CS hydrogel composite, it was cleaned with pure water and allowed to dry for a day at 40°C. The produced Lig-CS was then dissolved thoroughly by sonicating 100 mg of it in 50 mL of DI H₂O for 20 min at 60°C. Following ultrasonic irradiation, a freshly made HAuCl₄ solution (5 mM, 10 mL) was added to the medium and allowed to react for 60 min at 60°C. The solution’s color changed from translucent to dark pink during this process, signifying that Lig-CS/Au NPs were successfully prepared. After 5 min of centrifugation at 6000 rpm, followed by water rinsing and a 24 h drying period at 40°C, the Lig-CS/Au NPs were ultimately obtained.

2.3. Typical procedure for synthesis of biphenyls

Lig-CS/Au NPs (15 mg, 0.2 mol%), haloarenes (1 mmol), phenylboronic acid (1.1 mmol), a 5 mL combination of EtOH-H₂O (1:1), and K₂CO₃ (2 mmol) were added to a 25 mL balloon flask to start the reaction. For the necessary amount of time, the reaction mixture was swirled at 50°C. Centrifugation was used to isolate the catalyst after the reaction was finished, as determined by thin layer chromatography (TLC). After that, the associated products were removed. A combination of n-hexane and ethyl acetate (4:1) was used as the eluent in column chromatography to purify the intended product, which was then identified by ¹H and ¹³C NMR.

Characterized data for 4-methoxy-biphenyl: White crystal, Mp: 86-88°C; ¹H NMR (CDCl₃, 200 MHz): δ (ppm): 3.84 (3H, s, OCH₃); 6.96-.7.09(2H, d, Ar), 7.33-7.55 (7H, m, Ar); ¹³C NMR (CDCl3, 50 MHz): δ (ppm): 55.25 (OCH₃), 114.2, 126.7, 126.8, 128.2, 128.8, 133.6, 140.8, 159.0 (8C Ar).

2.4. Antioxidant activity evaluation

The antioxidant properties of Lig-CS/Au NPs were investigated using the well-known DPPH assay. For the experiment, DPPH powder was dissolved in EtOH (2 mg in 33.8 mL of 96% EtOH) and kept in the dark at 37°C for 30 min. It was then treated with various sample mixtures of different concentrations (1-1000 μg/mL of the NPs), allowing the solutions to remain in the dark for an additional hour before measuring absorbance. The appropriate DPPH ethanolic dilution produces a purple solution with the highest absorption at 517 nm. Following the interactions between the solution and nanoparticles, the absorbance gradually decreases due to the absorption of free radicals or protons from the sample. DPPH stabilizes by capturing an electron or a hydrogen atom. In this context, we employed butyl hydroxytoluene (BHT) as a standard antioxidant and calculated the inhibition percentage using Eq. (1).

(1)

I n h i b i t i o n (%) = (1 - \frac{A b s_{s a m p l e} - A b s_{b l a n k}}{A b s_{c o n t r o l} - A b s_{b l a n k}}) \times 100

2.5. Cytotoxicity activity evaluation

The cytotoxicity of the Lig-CS/Au NP nanocomposite was assessed using the MTT assay kit on HeLa, SiHa, and CCI-PI 19 cervical cancer cell lines. Initially, the cell lines were cultured according to standard procedures in a 96-well plate (1×10⁵ cells/well) and incubated in a humidified chamber at 37°C with 5% CO₂ for 24 h. Once the cell monolayer reached approximately 85% confluence, the growth medium (containing 10% fetal bovine serum (FBS)) was replaced with phosphate buffer saline (PBS). Meanwhile, the nano-sample was prepared in varying concentrations (0.5-1000 µg/mL) and suspended in RPMI medium. Following the addition of the nano-sample, the cultivated cells were incubated for 3 days in the same circumstances. Following this, each well received 10 µL of MTT dye (5 mg/mL in PBS) and was incubated for 4 h. After the incubation period, 100 µL of dimethyl sulfoxide (DMSO) was added to the medium, and the mixture was agitated to dissolve the formazan crystals. Lastly, a UV-Vis spectrophotometer was used to detect the absorbance of the resultant solution at 545 nm, and an enzyme-linked immunosorbent assay (ELISA) microplate reader was used for analysis.

2.6. Statistical analysis

All tests were statistically analyzed three times, and the one-way Analysis of variance (ANOVA) and LSD tests were used to assess the findings.

3. Results and Discussion

3.1. Characterization of Lig-CS/Au NPs nanocomposite

A straightforward and environmentally friendly method for creating Lig-CS/Au NPs in ultrasonic settings was presented. The lignin-chitosan composite, which includes functional groups rich in electrons like -OH and -NH, makes it easier to cap gold ions through coordination bonds. Under the impact of ultrasound [37,38], this mechanism allows for the reduction/stabilization of Au NPs [27,37] (Scheme 1). A variety of analytical methods were used to characterize and assess the physicochemical properties of the resultant Lig-CS/Au NPs. It was applied as a novel catalyst for Suzuki coupling reactions (Scheme 1). According to ICP-OES data, the nanocomposite contained 0.051 mmol/g of gold.

The XRD pattern of the Lig-CS/Au NPs was analyzed to confirm the reduction of Au (III) to Au (0) on the surface of Lig-CS; the findings have been shown in Figure 1. Four different peaks can be seen in the XRD result at 38.2°, 44.3°, 64.6°, and 77.6°. These peaks correspond to the Au nanoparticles’ (111), (200), (220), and (311) crystallographic planes. These distinct peaks offer compelling proof that the Lig-CS composite has stabilized Au NPs. The non-crystalline Lig-CS composite is responsible for the first phase seen in the 2θ range up to 22.2°.

XRD patterns of the (a) Lig-CS and (b) Lig-CS/Au NPs.

The reduction of Au³⁺ to Au⁰ can be confirmed by the UV-Vis spectra in addition to the visible color change (creation of a dark-pink tint from a colorless solution). Au NPs’ distinctive surface plasmon resonance (SPR) excitation peak can be seen in Figure 2 at a wavelength of about 545 nm.

UV-Vis spectra of (a) Lig-CS and (b) produced Lig-CS/Au NPs with its image (inset).

FE-SEM was used to examine the size, shape, and structural morphology of the produced Lig-CS and Lig-CS/Au NPs are as illustrated in Figure 3(a) and Figure 3(b). The particles’ pseudo-spherical shape is visible in the photograph. The existence of C, O, N, and Au in the nanocomposite’s elemental composition was verified by EDX analysis (Figure 3c), which also corroborated the composition of the Lig-CS/Au NPs. These findings were further supported by elemental mapping (Figure 4), which provided a detailed visualization of the distribution of the elements. X-ray scanning of the SEM image yielded the same elemental composition as observed in the EDX analysis. The colored dots in the mapping represent the respective elemental species, which are uniformly dispersed throughout the matrix.

(a,b) FE-SEM images of (a) Lig-CS, and (b) the Lig-CS/Au NPs with its (c) EDX pattern.

TEM images (Figure 5) were used to further analyze the structural properties of the Lig-CS/Au NPs. These pictures showed spherical, monodispersed Au NPs with an average particle diameter of roughly 5-10 nm. Furthermore, the Lig-CS polymers were seen to be surrounded by a gray layer around the Au NPs. For the Au NPs, these polymers serve as stabilizing and reducing agents. According to the TEM picture, the particle size histogram of the Au NPs has been shown in Figure 6 as 7.15 nm.

TEM images of the Lig-CS/Au NPs at different magnifications.

3.2. Catalytic application of Lig-CS/Au NPs

After thoroughly characterizing the Lig-CS/Au NP composite, its catalytic activity was investigated in the C-C bond construction via the Suzuki coupling (Scheme 1). Initially, it was essential to optimize the system using a probe reaction with 4-bromotoluene and phenylboronic acid. Table 1 summarizes the results of this optimization, examining various factors such as solvent, type of base, amount of catalyst, and medium temperature. The analysis of these parameters revealed that the model reaction yielded excellent results, with a high yield of the desired biphenyl. This was obtained using 15 mg of Lig-CS/Au NPs (0.2 mol% Au content), K₂CO₃ as the optimal base, and a solvent mixture of EtOH-H₂O (1:1) at 60°C under air (Table 1, entry 5).

Once optimal reaction conditions were established, the applicability and versatility of the Lig-CS/Au NPs catalyst across a broad range of arylhalides was assessed. Table 2 presents the various substrates tested in the coupling reactions, demonstrating that most of them exhibited excellent compatibility with the reaction conditions. Notably, chloroarenes, due to their weaker group leaving ability, reacted more slowly compared to bromo- or iodoarenes (Table 2, entries 3, 6, 9). In contrast, irrespective of the effect of other organic substituents, whether electron-donating (CH₃, OCH₃) or electron-withdrawing (COCH₃), all reactions produced high yields within 1-3 h.

Table 2. The Suzuki coupling catalyzed by Lig-CS/Au NPs.^a

Entry	RC₆H₄X	X	Time (h)	Yield (%)^b	TOF (h^-1)^c	TON (h^-1)^d
1	H	I	2	98	225	490
2	H	Br	3	96	160	480
3	H	Cl	12	50	20.8	250
4	4-Me	I	2	98	225	490
5	4-Me	Br	3	96	160	480
6	4-Me	Cl	12	50	20.8	250
7	4-COMe	I	2	96	240	480
8	4-COMe	Br	4	90	112.5	450
9	4-COMe	Cl	12	45	18.75	225
10	4-MeO	I	2	92	230	460
11	4-MeO	Br	3	90	150	450

^a 1.0 mmol arylhalide,1.0 mmolphenylboronic acid and 2 mmol K₂CO₃ in the presence of catalyst (0.2 mol% Au), 60 °C, 5 mL of EtOH-H₂O (1:1), aerobic conditions.

^b Isolated yield.

^c TOF, turnover frequencies (TOF) = (yield/time)/amount of catalyst (mol).

^d TON, turnover number (TON) = yield/amount of catalyst (mol).

To assess its recyclability, the heterogeneous Lig-CS/Au NP nanocomposite was isolated by centrifugation, thoroughly cleaned with ethanol, and dried at 60°C after the reaction concluded. Notably, the catalyst maintained its activity over seven cycles (Figure 7a) during stability testing. A hot filtration test further confirmed the catalyst’s robustness by centrifuging it from the reaction medium halfway through and allowing the reaction to proceed without the catalyst. Remarkably, there was no further progress in the reaction, indicating that no active species had leached from the catalyst. It was found to be catalytically inactive in the case of minor leaching. Additionally, the stability of the nanocatalyst was demonstrated by the TEM image of the recovered catalyst after the seventh run, confirming that the nanoparticles retained the same size as the fresh catalyst (Figure 7b).

(a) Recycling study of the catalyst for probe reaction, and (b) TEM image of reused catalyst after 7th run.

3.3. Evaluation of antioxidant and anti-cervical cancer effects of Lig-CS/Au NPs

Given our interest in exploring the anti-cervical cancer potential of the Lig-CS/Au NP nanocomposite, it was crucial to first evaluate its antioxidant properties. Effective antioxidants are known to significantly inhibit cancer cell proliferation and induce apoptosis. As previously mentioned, we performed the DPPH assay to assess the antioxidant activity of the nanocomposite. The material was introduced into the methanolic DPPH solution at seven different concentrations (31.25-1000 μg/mL). When the sample abstracts a proton or electron, DPPH undergoes reduction, which is visually indicated by a color shift from dark purple to light yellow. The change in absorbance was then measured spectrophotometrically at 517 nm. The antioxidant capacity, or scavenging activity, was quantified as the percentage of inhibition, calculated using Eq. (1). Figure 8 displays the corresponding scavenging capacity in terms of % inhibition of Lig-CS/Au NPs nanocomposite and the standard BHT at variable concentrations. The IC₅₀ values for BHT as standard and Lig-CS/Au NPs against DPPH free radicals in the antioxidant experiment were 102 µg/mL and 148 µg/mL, respectively.

Antioxidant potential of Lig-CS/Au NPs nanocomposite and BHT against DPPH.

The cytotoxicity of the Lig-CS/Au NPs was assessed using the MTT assay on three cervical cancer cell lines: HeLa, SiHa, and CCI-PI 19, at varying concentrations. The results, shown in Figure 9(a-c), clearly demonstrate that Lig-CS/Au NPs exhibit significant toxicity against all three cell lines, with toxicity increasing as the material concentration rises. Since cell viability is inversely proportional to toxicity, cell viability decreased as the concentration of the nanocomposite increased. The calculated IC₅₀ values were 454, 642, and 745 µg/mL for the respective cell lines. Notably, the Lig-CS/Au NP nanocomposite showed the highest inhibition against the HeLa cell line. Furthermore, the IC₅₀ of cisplatin as a standard anticancer drug, for HeLa, SiHa, and CCI-PI 19 cells were 169, 173, and 185 μg/mL, respectively. Additionally, cytotoxicity tests on the normal human cell line, HUVEC, revealed minimal effect, suggesting that Lig-CS/Au NPs are relatively safe for human cells (Figure 9d).

In vitro toxicity analysis of Lig-CS/Au NPs on (a) HeLa cell; (b) SiHa cell; (c) CCI-PI 19 cell and (d) HUVEC cell.

4. Conclusions

In summary, this study presented a green, environmentally friendly process for synthesizing bio-produced Au NPs encased in lignin-chitosan and exposed to ultrasonic radiation. The required Lig-CS/Au NP nanocomposite was identified using several sophisticated analytical techniques. The particles were round, monodispersed, and roughly 7.15 nm in size, according to TEM examination. Additionally, the produced Lig-CS/Au NPs were used as an effective catalyst for Suzuki coupling-based biphenyl synthesis. The antitumor potential of the Lig-CS/Au NP nanocomposite against human cervical carcinoma was studied. Prior to the cancer studies, its antioxidant activity was assessed using the DPPH method, which yielded significant IC₅₀ values. Following this, the material was tested for cytotoxicity against three cervical cancer cell lines, HeLa, SiHa, and CCI-PI 19, where promising IC₅₀ values were observed. The corresponding IC₅₀ values were found to be 454, 642, and 745 µg/mL, respectively. In addition, cytotoxicity tests on the normal human cell line, HUVEC, showed that Lig-CS/Au NPs are relatively safe for human cells. These results show that Lig-CS/Au NPs could be used as a strong candidate for further in vivo studies and may hold potential as a therapeutic agent for human cervical cancer.

Acknowledgment

Research Project of the Shanghai Municipal Health Commission (20214Y0289).

CRediT authorship contribution statement

Yun Xu, Ling Gao, Yi Guo: Visualization, Writing original draft, Formal analysis, Mengjiao Xu, Shu Shan, Demei Xin: Funding acquisition, Methodology, Supervision. Mengjiao Xu, Shu Shan, Demei Xin: Writing original draft, Formal analysis, Writing-review and editing. All authors reviewed the manuscript.

Declaration of competing interest

The authors report no conflicts of interest in this work.

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.

References

Chen L., Jiang Z., Yang L., Fang Y., Lu S., Akakuru O.U., Huang S., Li J., Ma S., Wu A.. HPDA/Zn as a CREB inhibitor for ultrasound imaging and stabilization of atherosclerosis plaque. Chinese Journal of Chemistry. 2023;41:199-206. https://doi.org/10.1002/cjoc.202200406
[Google Scholar]
Han L., Xu S., Zhou D., Chen R., Ding Y., Zhang M., Bao M., He B., Li S.. Unveiling the causal link between metabolic factors and ovarian cancer risk using Mendelian randomization analysis. Frontiers in Endocrinology. 2024;15:1401648. https://doi.org/10.3389/fendo.2024.1401648
[Google Scholar]
Wu N., Zhang X., Fang C., Zhu M., Wang Z., Jian L., Tan W., Wang Y., Li H., Xu X., Zhou Y., Chu T.Y., Wang J., Liao Q.. Progesterone enhances niraparib efficacy in ovarian cancer by promoting palmitoleic-acid-mediated ferroptosis. Research (Washington, D.C.). 2024;7:0371. https://doi.org/10.34133/research.0371
[Google Scholar]
Zeng G., Wu Z., Cao W., Wang Y., Deng X., Zhou Y.. Identification of anti-nociceptive constituents from the pollen of Typha angustifolia L. Using effect-directed fractionation. Natural Product Research. 2020;34:1041-1045. https://doi.org/10.1080/14786419.2018.1539979
[Google Scholar]
Shi S., Li K., Peng J., Li J., Luo L., Liu M., Chen Y., Xiang Z., Xiong P., Liu L., Cai W.. Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) A.C. Sm. by UHPLC-Q-exactive orbitrap mass spectrometry and assessment of their antioxidant and anti-inflammatory activities. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2022;149:112828. https://doi.org/10.1016/j.biopha.2022.112828
[Google Scholar]
Zhou J., Li H., Wu B., Zhu L., Huang Q., Guo Z., He Q., Wang L., Peng X., Guo T.. Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer. Scientific Reports. 2024;14:1860. https://doi.org/10.1038/s41598-024-52413-9
[Google Scholar]
Wang Y., Xu Y., Song J., Liu X., Liu S., Yang N., Wang L., Liu Y., Zhao Y., Zhou W., Zhang Y.. Tumor cell-targeting and tumor microenvironment–Responsive nanoplatforms for the multimodal imaging-guided photodynamic/photothermal/chemodynamic treatment of cervical cancer. International Journal of Nanomedicine. 2024;Volume 19:5837-5858. https://doi.org/10.2147/ijn.s466042
[Google Scholar]
Pang J., Ding N., Liu X., He X., Zhou W., Xie H., Feng J., Li Y., He Y., Wang S., Xiao Z.. Prognostic value of the baseline systemic immune-inflammation index in HER2-Positive metastatic breast cancer: Exploratory analysis of two prospective trials. Annals of Surgical Oncology. 2025;32:750-759. https://doi.org/10.1245/s10434-024-16454-8
[Google Scholar]
Zhou J., Guo Z., Peng X., Wu B., Meng Q., Lu X., Feng L., Guo T.. Chrysotoxine regulates ferroptosis and the PI3K/AKT/mTOR pathway to prevent cervical cancer. Journal of Ethnopharmacology. 2025;338:119126. https://doi.org/10.1016/j.jep.2024.119126
[Google Scholar]
Sheraz M., Sun X.F., Siddiqui A., Wang Y., Hu S., Sun R.. Cellulose-based electrochemical sensors. Sensors (Basel, Switzerland). 2025;25:645. https://doi.org/10.3390/s25030645
[Google Scholar]
Wang B., Yang G., Chen J., Fang G.. Green synthesis and characterization of gold nanoparticles using lignin nanoparticles. Nanomaterials (Basel, Switzerland). 2020;10:1869. https://doi.org/10.3390/nano10091869
[Google Scholar]
Priyadarshini E., Pradhan N.. Sensors and Actuators B: Chemical. 2017;238:888-902. https://doi.org/10.1016/j.snb.2016.06.081
Yu X., Luan S., Lei S., Huang J., Liu Z., Xue X., Ma T., Ding Y., Zhu B.. Deep learning for fast denoising filtering in ultrasound localization microscopy. Physics in Medicine and biology. 2023;68:205002. https://doi.org/10.1088/1361-6560/acf98f
[Google Scholar]
Dykman L., Khlebtsov N.. Chemical Society Reviews. 2012;41:2256-2282. https://doi.org/10.1039/C1CS15166E
Penn S.G., He L., Natan M.J.. Current Opinion in Chemical Biology. 2003;7:609-615. https://doi.org/10.1016/j.cbpa.2003.08.013
Prasad B.L.V., Savka S.I., Sorensen C.M., Zaikovaski V., Klabunde K.J.. Journal of the American Chemical Society. 2003;125:10488-10489. https://doi.org/10.1021/ja035046h
Wang Y., Xia S., Chen K., Zhang J., Yu C., Wu J., Wang P., Zhang W., Wu Y.. Balancing intermediates formation on atomically Pd-Bridged Cu/Cu₂O interfaces for kinetics-matching electrocatalytic C─N coupling reaction. Angewandte Chemie (International ed. in English). 2025;64:e202503011. https://doi.org/10.1002/anie.202503011
[Google Scholar]
Kreibig U., Vollmer M.. Optical Properties of Metal Clusters. Berlin: Springer-Verlag; 1995. https://doi.org/10.1007/978-3-662-09109-8
Smirnova N.V., Kolbe K.A., Dresvyanina E.N., Grebennikov S.F., Dobrovolskaya I.P., Yudin V.E., Luxbacher T., Morganti P.. Effect of chitin nanofibrils on biocompatibility and bioactivity of the chitosan-based composite film matrix intended for tissue engineering. Materials (Basel, Switzerland). 2019;12:1874. https://doi.org/10.3390/ma12111874
[Google Scholar]
Najafipour I., Emami N., Sadeh P., Amoli A., Mosleh-Shirazi S., Amani A.M., Kamyab H., Chelliapan S., Kasaee S.R., Vafa E.. Synthesis of Fe₃O₄@MIL-101-OH/Chitosan for adsorption and release of doxorubicin. Polymer Testing. 2025;142:108659. https://doi.org/10.1016/j.polymertesting.2024.108659
[Google Scholar]
Pogorielov M.V., Sikora V.Z.. Chitosan as a hemostatic agent: Current state. European Journal of Medicine Series B. 2015;2:24. http://dx.doi.org/10.13187/ejm.s.b.2015.2.24
[Google Scholar]
Thakur V.K., Thakur M.K.. Recent advances in graft copolymerization and applications of chitosan: A review. ACS Sustainable Chemistry & Engineering. 2014;2:2637-2652. https://doi.org/10.1021/sc500634p
[Google Scholar]
Pinheiro A.C., Bourbon A.I., Quintas M.A.C., Coimbra M.A., Vicente A.A.. K-carrageenan/chitosan nanolayered coating for controlled release of a model bioactive compound. Innovative Food Science & Emerging Technologies. 2012;16:227. https://doi.org/10.1016/j.ifset.2012.06.004
[Google Scholar]
Musilová L., Mráček A., Kovalcik A., Smolka P., Minařík A., Humpolíček P., Vícha R., Ponížil P.. Hyaluronan hydrogels modified by glycinated Kraft lignin: Morphology, swelling, viscoelastic properties and biocompatibility. Carbohydrate Polymers. 2018;181:394-403. https://doi.org/10.1016/j.carbpol.2017.10.048
[Google Scholar]
Xu Y., Fan Z., Li X., Yang S., Wang J., Zheng A., Shu R.. Cooperative production of monophenolic chemicals and carbon adsorption materials from cascade pyrolysis of acid hydrolysis lignin. Bioresource Technology. 2024;399:130557. https://doi.org/10.1016/j.biortech.2024.130557
[Google Scholar]
Spiridon I., Tanase C.E.. Design, characterization and preliminary biological evaluation of new lignin-PLA biocomposites. International Journal of Biological Macromolecules. 2018;114:855-863. https://doi.org/10.1016/j.ijbiomac.2018.03.140
[Google Scholar]
Pettersen R.O.G.E.R.C.. The chemical composition of wood. In: Advances in Chemistry”,”The Chemistry of Solid Wood. Washington, DC: American Chemical Society; p. :57-126. https://doi.org/10.1021/ba-1984-0207.ch002
[Google Scholar]
Dallmeyer I., Chowdhury S., Kadla J.F.. Preparation and characterization of Kraft lignin-based moisture-responsive films with reversible shape-change capability. Biomacromolecules. 2013;14:2354-2363. https://doi.org/10.1021/bm400465p
[Google Scholar]
Crouvisier-Urion K., Lagorce-Tachon A., Lauquin C., Winckler P., Tongdeesoontorn W., Domenek S., Debeaufort F., Karbowiak T.. Impact of the homogenization process on the structure and antioxidant properties of chitosan-lignin composite films. Food Chemistry. 2017;236:120-126. https://doi.org/10.1016/j.foodchem.2017.03.094
[Google Scholar]
Slocik J.M., Naik R.R., Stone M.O., Wright D.W.. Journal of Materials Chemistry. 2005;15:749-753. https://doi.org/10.1002/smll.200500172
Tamaoand K., Miyaura N.. Topics in Current Chemistry. 2002;219:1. https://www.amazon.co.jp/-/en/Norio-Miyaura/dp/3540421750
Miyaura N., Suzuki A.. Chemical Reviews. 1995;95:2457-2483. https://doi.org/10.1021/cr00039a007
Hassan J., Sevignon M., Gozzi C., Schulz E., Lemaire M.. Chemical Reviews. 2002;102:1359-1470. https://doi.org/10.1021/cr000664r
Martinand R., Buchwald S.L.. Accounts of Chemical Research. 2008;41:1461-1473. https://doi.org/10.1021/ar800036s
Thathagar M.B., Beckers J., Rothenberg G.J.. American Chemical Society. 2002;124:11858-11859. https://doi.org/10.1021/ja027716+
Huang T., Liu J., Guan Y.S.ong, Zheng J., El-kott A.F., Negm S.. Decoration of silver nanoparticles over chitosan-Arabic gum hydrogel: Synthesis, characterization and investigation of its antioxidant and anti-colorectal cancer activities. Journal of Molecular Structure. 2025;1319:139541. https://doi.org/10.1016/j.molstruc.2024.139541
[Google Scholar]
Bährle C., Nick T.U., Bennati M., Jeschke G., Vogel F.. High-field electron paramagnetic resonance and density functional theory study of stable organic radicals in lignin: Influence of the extraction process, botanical origin, and protonation reactions on the radical g tensor. The Journal of Physical Chemistry. A. 2015;119:6475-6482. https://doi.org/10.1021/acs.jpca.5b02200
[Google Scholar]
Fuentes-García J.A., Santoyo-Salzar J., Rangel-Cortes E., Goya G.F., Cardozo-Mata V., Pescador-Rojas J.A.. Effect of ultrasonic irradiation power on sonochemical synthesis of gold nanoparticles. Ultrasonics Sonochemistry. 2021;70:105274. https://doi.org/10.1016/j.ultsonch.2020.105274
[Google Scholar]

1. Introduction

2. Materials and Methods

2.1. Material and methods
2.2. Lig-CS/Au NPs nanocomposite synthesis
2.3. Typical procedure for synthesis of biphenyls
2.4. Antioxidant activity evaluation
2.5. Cytotoxicity activity evaluation
2.6. Statistical analysis

3. Results and Discussion

3.1. Characterization of Lig-CS/Au NPs nanocomposite
3.2. Catalytic application of Lig-CS/Au NPs
3.3. Evaluation of antioxidant and anti-cervical cancer effects of Lig-CS/Au NPs

4. Conclusions

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[1] Chen L., Jiang Z., Yang L., Fang Y., Lu S., Akakuru O.U., Huang S., Li J., Ma S., Wu A.. HPDA/Zn as a CREB inhibitor for ultrasound imaging and stabilization of atherosclerosis plaque. Chinese Journal of Chemistry. 2023;41:199-206. https://doi.org/10.1002/cjoc.202200406
[Google Scholar]

[2] Han L., Xu S., Zhou D., Chen R., Ding Y., Zhang M., Bao M., He B., Li S.. Unveiling the causal link between metabolic factors and ovarian cancer risk using Mendelian randomization analysis. Frontiers in Endocrinology. 2024;15:1401648. https://doi.org/10.3389/fendo.2024.1401648
[Google Scholar]

[3] Wu N., Zhang X., Fang C., Zhu M., Wang Z., Jian L., Tan W., Wang Y., Li H., Xu X., Zhou Y., Chu T.Y., Wang J., Liao Q.. Progesterone enhances niraparib efficacy in ovarian cancer by promoting palmitoleic-acid-mediated ferroptosis. Research (Washington, D.C.). 2024;7:0371. https://doi.org/10.34133/research.0371
[Google Scholar]

[4] Zeng G., Wu Z., Cao W., Wang Y., Deng X., Zhou Y.. Identification of anti-nociceptive constituents from the pollen of Typha angustifolia L. Using effect-directed fractionation. Natural Product Research. 2020;34:1041-1045. https://doi.org/10.1080/14786419.2018.1539979
[Google Scholar]

[5] Shi S., Li K., Peng J., Li J., Luo L., Liu M., Chen Y., Xiang Z., Xiong P., Liu L., Cai W.. Chemical characterization of extracts of leaves of Kadsua coccinea (Lem.) A.C. Sm. by UHPLC-Q-exactive orbitrap mass spectrometry and assessment of their antioxidant and anti-inflammatory activities. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2022;149:112828. https://doi.org/10.1016/j.biopha.2022.112828
[Google Scholar]

[6] Zhou J., Li H., Wu B., Zhu L., Huang Q., Guo Z., He Q., Wang L., Peng X., Guo T.. Network pharmacology combined with experimental verification to explore the potential mechanism of naringenin in the treatment of cervical cancer. Scientific Reports. 2024;14:1860. https://doi.org/10.1038/s41598-024-52413-9
[Google Scholar]

[7] Wang Y., Xu Y., Song J., Liu X., Liu S., Yang N., Wang L., Liu Y., Zhao Y., Zhou W., Zhang Y.. Tumor cell-targeting and tumor microenvironment–Responsive nanoplatforms for the multimodal imaging-guided photodynamic/photothermal/chemodynamic treatment of cervical cancer. International Journal of Nanomedicine. 2024;Volume 19:5837-5858. https://doi.org/10.2147/ijn.s466042
[Google Scholar]

[8] Pang J., Ding N., Liu X., He X., Zhou W., Xie H., Feng J., Li Y., He Y., Wang S., Xiao Z.. Prognostic value of the baseline systemic immune-inflammation index in HER2-Positive metastatic breast cancer: Exploratory analysis of two prospective trials. Annals of Surgical Oncology. 2025;32:750-759. https://doi.org/10.1245/s10434-024-16454-8
[Google Scholar]

[9] Zhou J., Guo Z., Peng X., Wu B., Meng Q., Lu X., Feng L., Guo T.. Chrysotoxine regulates ferroptosis and the PI3K/AKT/mTOR pathway to prevent cervical cancer. Journal of Ethnopharmacology. 2025;338:119126. https://doi.org/10.1016/j.jep.2024.119126
[Google Scholar]

[10] Sheraz M., Sun X.F., Siddiqui A., Wang Y., Hu S., Sun R.. Cellulose-based electrochemical sensors. Sensors (Basel, Switzerland). 2025;25:645. https://doi.org/10.3390/s25030645
[Google Scholar]

[11] Wang B., Yang G., Chen J., Fang G.. Green synthesis and characterization of gold nanoparticles using lignin nanoparticles. Nanomaterials (Basel, Switzerland). 2020;10:1869. https://doi.org/10.3390/nano10091869
[Google Scholar]

[12] Priyadarshini E., Pradhan N.. Sensors and Actuators B: Chemical. 2017;238:888-902. https://doi.org/10.1016/j.snb.2016.06.081

[13] Yu X., Luan S., Lei S., Huang J., Liu Z., Xue X., Ma T., Ding Y., Zhu B.. Deep learning for fast denoising filtering in ultrasound localization microscopy. Physics in Medicine and biology. 2023;68:205002. https://doi.org/10.1088/1361-6560/acf98f
[Google Scholar]

[14] Dykman L., Khlebtsov N.. Chemical Society Reviews. 2012;41:2256-2282. https://doi.org/10.1039/C1CS15166E

[15] Penn S.G., He L., Natan M.J.. Current Opinion in Chemical Biology. 2003;7:609-615. https://doi.org/10.1016/j.cbpa.2003.08.013

[16] Prasad B.L.V., Savka S.I., Sorensen C.M., Zaikovaski V., Klabunde K.J.. Journal of the American Chemical Society. 2003;125:10488-10489. https://doi.org/10.1021/ja035046h

[17] Wang Y., Xia S., Chen K., Zhang J., Yu C., Wu J., Wang P., Zhang W., Wu Y.. Balancing intermediates formation on atomically Pd-Bridged Cu/Cu₂O interfaces for kinetics-matching electrocatalytic C─N coupling reaction. Angewandte Chemie (International ed. in English). 2025;64:e202503011. https://doi.org/10.1002/anie.202503011
[Google Scholar]

[18] Kreibig U., Vollmer M.. Optical Properties of Metal Clusters. Berlin: Springer-Verlag; 1995. https://doi.org/10.1007/978-3-662-09109-8

[19] Smirnova N.V., Kolbe K.A., Dresvyanina E.N., Grebennikov S.F., Dobrovolskaya I.P., Yudin V.E., Luxbacher T., Morganti P.. Effect of chitin nanofibrils on biocompatibility and bioactivity of the chitosan-based composite film matrix intended for tissue engineering. Materials (Basel, Switzerland). 2019;12:1874. https://doi.org/10.3390/ma12111874
[Google Scholar]

[20] Najafipour I., Emami N., Sadeh P., Amoli A., Mosleh-Shirazi S., Amani A.M., Kamyab H., Chelliapan S., Kasaee S.R., Vafa E.. Synthesis of Fe₃O₄@MIL-101-OH/Chitosan for adsorption and release of doxorubicin. Polymer Testing. 2025;142:108659. https://doi.org/10.1016/j.polymertesting.2024.108659
[Google Scholar]

[21] Pogorielov M.V., Sikora V.Z.. Chitosan as a hemostatic agent: Current state. European Journal of Medicine Series B. 2015;2:24. http://dx.doi.org/10.13187/ejm.s.b.2015.2.24
[Google Scholar]

[22] Thakur V.K., Thakur M.K.. Recent advances in graft copolymerization and applications of chitosan: A review. ACS Sustainable Chemistry & Engineering. 2014;2:2637-2652. https://doi.org/10.1021/sc500634p
[Google Scholar]

[23] Pinheiro A.C., Bourbon A.I., Quintas M.A.C., Coimbra M.A., Vicente A.A.. K-carrageenan/chitosan nanolayered coating for controlled release of a model bioactive compound. Innovative Food Science & Emerging Technologies. 2012;16:227. https://doi.org/10.1016/j.ifset.2012.06.004
[Google Scholar]

[24] Musilová L., Mráček A., Kovalcik A., Smolka P., Minařík A., Humpolíček P., Vícha R., Ponížil P.. Hyaluronan hydrogels modified by glycinated Kraft lignin: Morphology, swelling, viscoelastic properties and biocompatibility. Carbohydrate Polymers. 2018;181:394-403. https://doi.org/10.1016/j.carbpol.2017.10.048
[Google Scholar]

[25] Xu Y., Fan Z., Li X., Yang S., Wang J., Zheng A., Shu R.. Cooperative production of monophenolic chemicals and carbon adsorption materials from cascade pyrolysis of acid hydrolysis lignin. Bioresource Technology. 2024;399:130557. https://doi.org/10.1016/j.biortech.2024.130557
[Google Scholar]

[26] Spiridon I., Tanase C.E.. Design, characterization and preliminary biological evaluation of new lignin-PLA biocomposites. International Journal of Biological Macromolecules. 2018;114:855-863. https://doi.org/10.1016/j.ijbiomac.2018.03.140
[Google Scholar]

[27] Pettersen R.O.G.E.R.C.. The chemical composition of wood. In: Advances in Chemistry”,”The Chemistry of Solid Wood. Washington, DC: American Chemical Society; p. :57-126. https://doi.org/10.1021/ba-1984-0207.ch002
[Google Scholar]

[28] Dallmeyer I., Chowdhury S., Kadla J.F.. Preparation and characterization of Kraft lignin-based moisture-responsive films with reversible shape-change capability. Biomacromolecules. 2013;14:2354-2363. https://doi.org/10.1021/bm400465p
[Google Scholar]

[29] Crouvisier-Urion K., Lagorce-Tachon A., Lauquin C., Winckler P., Tongdeesoontorn W., Domenek S., Debeaufort F., Karbowiak T.. Impact of the homogenization process on the structure and antioxidant properties of chitosan-lignin composite films. Food Chemistry. 2017;236:120-126. https://doi.org/10.1016/j.foodchem.2017.03.094
[Google Scholar]

[30] Slocik J.M., Naik R.R., Stone M.O., Wright D.W.. Journal of Materials Chemistry. 2005;15:749-753. https://doi.org/10.1002/smll.200500172

[31] Tamaoand K., Miyaura N.. Topics in Current Chemistry. 2002;219:1. https://www.amazon.co.jp/-/en/Norio-Miyaura/dp/3540421750

[32] Miyaura N., Suzuki A.. Chemical Reviews. 1995;95:2457-2483. https://doi.org/10.1021/cr00039a007

[33] Hassan J., Sevignon M., Gozzi C., Schulz E., Lemaire M.. Chemical Reviews. 2002;102:1359-1470. https://doi.org/10.1021/cr000664r

[34] Martinand R., Buchwald S.L.. Accounts of Chemical Research. 2008;41:1461-1473. https://doi.org/10.1021/ar800036s

[35] Thathagar M.B., Beckers J., Rothenberg G.J.. American Chemical Society. 2002;124:11858-11859. https://doi.org/10.1021/ja027716+

[36] Huang T., Liu J., Guan Y.S.ong, Zheng J., El-kott A.F., Negm S.. Decoration of silver nanoparticles over chitosan-Arabic gum hydrogel: Synthesis, characterization and investigation of its antioxidant and anti-colorectal cancer activities. Journal of Molecular Structure. 2025;1319:139541. https://doi.org/10.1016/j.molstruc.2024.139541
[Google Scholar]

[37] Bährle C., Nick T.U., Bennati M., Jeschke G., Vogel F.. High-field electron paramagnetic resonance and density functional theory study of stable organic radicals in lignin: Influence of the extraction process, botanical origin, and protonation reactions on the radical g tensor. The Journal of Physical Chemistry. A. 2015;119:6475-6482. https://doi.org/10.1021/acs.jpca.5b02200
[Google Scholar]

[38] Fuentes-García J.A., Santoyo-Salzar J., Rangel-Cortes E., Goya G.F., Cardozo-Mata V., Pescador-Rojas J.A.. Effect of ultrasonic irradiation power on sonochemical synthesis of gold nanoparticles. Ultrasonics Sonochemistry. 2021;70:105274. https://doi.org/10.1016/j.ultsonch.2020.105274
[Google Scholar]

Ultrasound assisted preparation of lignin-chitosan capped gold nanoparticles: Its evaluation for suzuki coupling and treatment of cervical cancer

Abstract

Keywords

Anti-cervical cancer

Chitosan

Gold nanoparticles

Lignin

Suzuki–miyaura

1. Introduction

2. Materials and Methods

2.1. Material and methods

2.2. Lig-CS/Au NPs nanocomposite synthesis

2.3. Typical procedure for synthesis of biphenyls

2.4. Antioxidant activity evaluation

2.5. Cytotoxicity activity evaluation

2.6. Statistical analysis

3. Results and Discussion

3.1. Characterization of Lig-CS/Au NPs nanocomposite

3.2. Catalytic application of Lig-CS/Au NPs

3.3. Evaluation of antioxidant and anti-cervical cancer effects of Lig-CS/Au NPs

4. Conclusions

Acknowledgment

CRediT authorship contribution statement

Declaration of competing interest

Declaration of Generative AI and AI-assisted technologies in the writing process

References

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