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Scientific Reports · 2026 · IF 4.9

Protein-free colorimetric biosensor for sensitive detection of HPV-18 mRNA via MNAzyme-driven catalytic hairpin assembly

Wang Yingnan,Wang Chang,Zhai Lin,Zhu Xiaoye

Cervical cancer is significantly associated with persistent infection of human papillomavirus (HPV) type 18, making accurate detection of low-abundance HPV-18 mRNA crucial for diagnosis and treatment. Current nucleic acid detection methods are often limited by complex instrumentation, time-consuming procedures, or fluorophore modifications. To address this, we developed an enzyme-free colorimetric biosensor by integrating a multicomponent nucleic acid enzyme (MNAzyme) with catalytic hairpin assembly (CHA) for signal amplification. In this strategy, target recognition triggers the formation of an active MNAzyme that cleaves a substrate hairpin, initiating a CHA cascade which releases G-rich sequences. These sequences form G-quadruplexes with peroxidase-like activity, catalyzing the oxidation of colorless TMB into a soluble blue product, enabling both visual detection and spectrophotometric quantification at 650 nm. Under optimized conditions, the biosensor achieved a detection limit of 6.92 pM for HPV-18 mRNA, allowing naked-eye identification of target levels as low as 10 pM. The platform exhibited high specificity and could be adapted to detect other HPV mRNA subtypes by simply modifying the recognition sequence. This work presents a universal, simplified, and sensitive colorimetric strategy with great promise for future development of point-of-care testing and viral analysis platforms.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Supramolecular Antigen Peptide Nanoparticles for Enhanced Photodynamic Therapy and Immunotherapy against Tumors

Ya Zhang,Jianwei Bao,Chen Jiang,Yuhong Liu,Shasha Peng,Qianli Zou

Antigen peptide-based immunotherapy holds significant promise for tumor treatment by eliciting targeted immune responses against tumor cells. However, current methods often face limitations in achieving effective antigen delivery and immune activation. Addressing these challenges through novel delivery systems and immunomodulatory strategies is crucial for improving the clinical efficacy of this therapy. Herein, a supramolecular system based on the self-assembly of the human papillomavirus (HPV) E7 antigen peptide is established by utilizing a Schiff base-mediated self-assembly approach. The E7 antigen peptide nanoparticles (E7 NPs) are further functionalized by loading chlorin e6 (Ce6) and decorating with bovine serum albumin (BSA), generating BSA/E7/Ce6 NPs. The BSA/E7/Ce6 NPs exhibited remarkable photodynamic effects in the inhibition of tumor cells and significantly improved tumor accumulation. Especially, the BSA/E7/Ce6 NPs improved antitumor immune responses of the E7 antigen by effectively activating cytotoxic T lymphocytes. The combination therapy integrating BSA/E7/Ce6 NPs with photodynamic therapy demonstrated a 1.8-fold increase in CD3+CD8+ T cells compared to monotherapy groups, leading to significantly enhanced antitumor effects. Our findings demonstrate that supramolecular antigen peptide nanomaterials can be established as drug delivery systems while retaining their original antigenicity, providing a versatile strategy for realizing enhanced antitumor immunotherapy.

CAS / MDL: 67-68-5
研究领域: 肿瘤学 · 免疫学 · 纳米医学
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CHEMICAL ENGINEERING JOURNAL · 2025 · IF 13.2

CuFe2O4@T-COF nanosphere-mediated biosensing platform based on DNA walker signal amplification strategy for ultrasensitive HPV detection

Zhen Yu,Yan Zhang,Dongquan Leng,Tingting Wu,Si-Jia Ge,Dawei Fan,Hongmin Ma,Yu Du,Qin Wei

Human papillomavirus (HPV) infection represents a major global health concern due to its strong association with cervical cancer and other malignancies, underscoring the critical need for highly sensitive detection methods. In this study, an advanced photoelectrochemical biosensing platform was developed for ultrasensitive HPV detection. An In 2 S 3 -sensitized SnO 2 heterostructure substrate that dramatically enhances photogenerated charge separation efficiency, generating extremely significant photocurrent enhancement. Furthermore, a CuFe 2 O 4 @T-COF nanosphere serving as a multifunctional signal quencher through synergistic steric hindrance, competitive oxygen consumption and light absorption effects. Notably, an exonuclease III-powered DNA walker system enabling cyclic signal amplification through programmable target recycling. The biosensor demonstrates exceptional analytical performance, achieving a broad dynamic range of 10 −6 to 10 μmol/L with an ultralow detection limit of 1.37 × 10 −7  μmol/L. This breakthrough sensing platform not only provides a powerful tool for early HPV diagnosis but also opens new possibilities for developing next-generation biosensors with clinical-level sensitivity and specificity.

研究领域: 生物传感器 · 纳米技术 · 分子诊断 · 病毒学 · 癌症研究 · 分析化学
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Advanced Healthcare Materials · 2025 · IF 9.6

NIR-Triggered Metal-Polyphenol Nanoparticles Enhance HPV-Driven Cancer Immunotherapy via Immunogenic Cell Death and STING Sequential Activation

Maoyu Liu,Jindong Zhang,Shuning Chen,Jiao Zheng,Linlin Xiao,Xiaoli Liu,Yang Cao,Shenyin Zhu,Shufang Chang

HPV-associated malignancies consistently express E6/E7 oncoproteins, making these viral antigens prime targets for therapeutic vaccination. However, insufficient antigen exposure and presentation remain major obstacles for potent immunotherapy. Here, a novel metal-polyphenol network-coated human serum albumin nanoplatform (IMT@H) is engineered to co-deliver IR780 and manganese ions (Mn 2+ ) to achieve enhanced immunogenic cell death (ICD) and cGAS-STING-dependent antigen presentation. The metal-polyphenol nanostructure facilitates the pH-responsive release of Mn 2+ , which subsequently initiates Fenton-like reactions to generate hydroxyl radicals (·OH). Meanwhile, under near-infrared (NIR) light irradiation, IR780 induces mitochondrial-targeted phototherapy and concurrently produces reactive oxygen species (ROS). These processes act synergistically to amplify the oxidative damage and ICD in TC-1 tumors, leading to the release of damage-associated molecular patterns (DAMPs). These ICD-derived DAMPs cooperate with Mn 2+ to sustain activation of the cGAS-STING pathway in dendritic cells. This combinatorial strategy successfully transforms tumor antigens into endogenous vaccines, eventually inhibiting the growth of primary tumors and producing strong abscopal effects. Notably, mice primed with nanovaccines exhibit strong anti-HPV16 E7-specific immune responses and tumor resistance. With its dual therapeutic and preventive functionality, IMT@H represents a paradigm-shifting strategy for virus-driven malignancies and offers a blueprint for engineering self-adjuvanting nanovaccines against viral oncogenesis.

CAS / MDL: 13446-34-9 1401-55-4
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Nanomaterials · 2022 ·Vol. 12 ·期 5 ·736 · IF 5.719

A Visual Discrimination of Existing States of Virus Capsid Protein by a Giant Molybdate Cluster

Yarong Xue,Mingfen Wei,Dingyi Fu,Yuqing Wu,Bo Sun,Xianghui Yu,Lixin Wu

We report a unique phenomenon, the opposite color response of a giant polyoxometalate, (NH4)42[Mo132O372(CHCOO)30] (H2O)72([Mo132]), to the existing states of human papillomavirus (HPV) major capsid protein, L1-pentamer (L1-p), and virus-like particles (VLPs). The color responses originate from the different assembly forms between [Mo132] and the capsid protein. The latter were inspected and separated by using CsCl gradient centrifugation, and validated in detail by sodium dodecyl sulfate-polyacrylamide gel-electrophoresis (SDS-PAGE), dynamic light scattering (DLS), and transmission electron microscopy (TEM) imaging. Furthermore, the intrinsic mechanisms were investigated in-depth by using XPS-based semi-quantitative analysis and well-designed peptides, revealing the critical points of L1 that determine the charge–transfer ratio between Mo(V) to Mo(VI), and consequently, the levels of [Mo132] hypochromic in different assemblies. Such a unique phenomenon is significant as it supplies a colorimetry approach to distinguish the existing states of the HPV capsid protein and would be significant in the quality assay of the HPV vaccine and existing states of other viruses in the future.Keywords:colorimetric discrimination;giant polyoxometalate;HPV capsid protein;hypochromic of molybdate clusters;opposite color response

CAS / MDL: 7647-14-5 1132-61-2
研究领域: 化学 · 病毒学 · 材料科学
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Frontiers in Pharmacology · 2021 · IF 5.811

Hydroxypropyl-β-Cyclodextrin-Complexed Resveratrol Enhanced Antitumor Activity in a Cervical Cancer Model: In Vivo Analysis

Hao Xincai,Sun Xiaodong,Zhu Haizhen,Xie Lixia,Wang Xuanbin,Jiang Nan,Fu Pan,Sang Ming

Trans-resveratrol (RES) exhibits a wide range of biological activities. Various methodological approaches have been established to improve the pharmacokinetic properties of RES. Moreover, additional in vivo studies are required to support clinical application. In this study, RES/HP-β-CD (RHSD) inclusion complex was prepared and characterized by FTIR, PXRD, DSC and NMR data. The effect and potential mechanism of RHSD against cervical cancer were investigated in a mouse xenograft tumor model by qPCR assay, Western blot assay, and immunohistochemical assay. Results showed that RHSD significantly decreased tumor growth compared with free RES, while the effect of preventing tumor growth was more prominent in vivo. Notably, RHSD could inhibit tumor development by suppressing the expression of HPV E6 and E7 oncogenes and upregulating P53 and Rb1 protein in cervical cancer. These findings demonstrated that RHSD was safe and potential for development of a new oral administration drug to treat cervical cancer.

CAS / MDL: 10102-40-6
研究领域: 药理学 · 肿瘤学 · 药物递送系统
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ANALYST · 2019 ·Vol. 144 ·期 9 ·2929-2935 · IF 4.019

Ultrasensitive SERS detection of specific oligonucleotides based on Au@AgAg bimetallic nanorods

Cui-Fang Ning,Ya-Fei Tian,Wen Zhou,Bin-Cheng Yin,Bang-Ce Ye

We synthesized a novel and sensitive Au/Ag bimetallic SERS-active nanotag, Au–Ag–Ag core–shell–shell nanorod (Au@AgAgNR). The Au@AgAgNR nanotag exhibited a strong SERS signal and was easily assembled from bilayer silver shells on an Au nanorod (AuNR) core with embedded Raman reporter molecules in the core–shell–shell gaps. The SERS activity of the nanotags was investigated with 2-mercaptopyridine (2-Mpy) as a Raman reporter, which could form pyridine/Ag+ coordination complexes to mediate the formation of silver shells. Specific enhancement of Raman signals was observed in the following order: AuNR < Au@AgNR < Au@AgAgNR. Then, Au@AgAgNR nanotags were coupled with magnetic beads (MBs) via specific DNA hybridization as a SERS sensor with a detection limit of 1 fM for a segment of the gene HPV-16. Factors affecting sensitivity and selectivity were investigated, including Raman dye concentration, silver nitrate dosage and the response to similar oligonucleotides. The proposed SERS sensor is expected to be a facile and sensitive method for specific gene detection.

CAS / MDL: 9005-64-5 57-09-0
研究领域: 分析化学 · 生物医学工程 · 纳米技术
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ACS Applied Materials & Interfaces · 2026 · IF 8.2

Galectin-1-Targeted Type-I/II Photosensitizers Activate the NF-κB Pathway to Enhance Immunity and Treat High-Risk HPV-Associated Cervical Lesions

Qianjun Su,Hui Duan,Qiyan Li,Mengdan Zhang,Pan Liu,Huixue Chen,Weili Li,Ping Liu,Chunlin Chen,Ruiyuan Liu,Pengfei Li

Persistent infection with high-risk HPV in women can progress to cervical intraepithelial neoplasia and even cervical cancer. This study investigated the cytotoxic and immunomodulatory effects of the TBTCN-TDG photodynamic therapy (PDT) probe in treating HPV-associated cervical lesions. The TBTCN-TDG probe was designed by integrating a donor-acceptor-π-acceptor 1 (D-A-π-A1) structure (TBTCN) with TDG, a moiety targeting Galectin-1, and its targeting ability in HPV-positive SiHa cells was confirmed. The in vitro results demonstrated that TBTCN-TDG combined with light treatment significantly inhibited SiHa cell proliferation, increased apoptosis, and activated immune responses by stimulating dendritic cells, macrophages, and NK cells, through enhanced NF-κB pathway signaling. In vivo, this targeted photosensitizer exhibited substantial therapeutic effects under laser excitation, as evidenced by TUNEL staining, which showed increased apoptosis in lesions. Immune analysis indicated that TBTCN-TDG enhanced NK cell viability and elevated the levels of pro-inflammatory cytokines under laser excitation, such as TNF-α, IFN-γ, and IL-6, confirming immune response activation. In conclusion, the combination of TBTCN-TDG and PDT effectively targets cells infected with HPV, enhances immune responses, and suppresses HPV infection. This suggests a novel therapeutic strategy for photodynamic immunotherapy in patients with cervical high-risk HPV infections.

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ADVANCED FUNCTIONAL MATERIALS · 2024 · IF 18.5

Thermally Engineered Ferric Yolk-Shells for Vaginal Secretion Based Cervical Cancer Screening

Jiao Wu,Yingting Wei,Chunjing Shi,Yida Huang,Zubei Hong,Wanshan Liu,Liying Gu,Ruimin Wang,Yuling Li,Jing Cao,Wen Di,Xumin Hou,Jian Liu,Kun Qian,Lihua Qiu

Engineering of materials is crucial for the advanced detection of bio-molecules, particularly in laser desorption/ionization mass spectrometry (LDI-MS). However, effective screening with enhanced LDI performance remains challenging due to the lack of engineered substrate materials. Herein, thermally engineered ferric yolk-shells are designed for enhanced metabolic screening of cervical cancer (CC) using vaginal secretion. A facile thermal engineering strategy is developed to prepare amorphous ferric yolk-shells with integrated properties. Notably, the amorphous mesoporous yolk-shells offer signal amplification up to orders of magnitude in LDI-MS for standard metabolites and diverse bio-samples. High-performance CC screening (including identification of human papillomavirus (HPV) infection, high-grade squamous intraepithelial lesion (HSIL), and CC) is achieved, with the areas under the curve of 0.842–0.963. Finally, a metabolic panel for CC screening, covering the stages of HPV, HSIL, and CC, is established. This work elucidates the LDI-MS mechanism for enhanced metabolic detection and highlights potential applications in cancer screening.

研究领域: 材料科学 · 癌症筛查 · 质谱分析 · 生物医学工程
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Frontiers in Chemistry · 2022 · IF 5.545

Green synthesis, structure optimization and biological evalution of Rhopaladins' analog 2-styryl-5-oxopyrrolidine-2- carboxamide RPDPRH on CaSki cells.

Li-Na Ke,Ling-Qi Kong,Xiu-Lian Zhu,Feng-Xu Wu,Qin-Hua Chen,Bin Li,Yun Dong,Hong-Mei Wang,Xiao-Hua Zeng

We have synthesized Rhopaladins’ analog (2E,4E)-4-chlorobenzylidene-2-(4-chlorostyryl)-N-cyclohexyl-1-(4-fluorophenyl)-5-oxopyrrolidine-2-carboxamide (RPDPRH) via a highly facile, inexpensive and green approach and verified the structural superiority of compound RPDPRH through molecular docking. Moreover, we further detected the anti-proliferation, apoptosis and HPV E6/E7 effects of RPDPRH on CaSki cells. Finally, we confirmed that compared with the previous compound (E)-N-(tert-butyl)-2-(4-chlorobenzoyl)-4-(4-fluorobenzylidene)-1-isopropyl-5-oxopyrrolidine-2-carboxamide (RPDPB), RPDPRH could better inhibit proliferation, induce apoptosis, and down-regulate HPV E6/E7 mRNA expression on Caski cells. And preliminary RT-PCR experiments have demonstrated that RPDPRH also could affect the expression of Bcl-2, Bax and Caspase-3 mRNA in Caski cells. In summary, RPDPRH has potential as an effective agent against cervical cancer and will play an important role in our subsequent research.Keywords: 4-arylidene-5-oxopyrrolidine, green synthesis, molecular docking, anti-tumor activity, apoptosis

CAS / MDL: 14913-33-8
研究领域: 化学 · 药理学 · 肿瘤学 · 分子生物学
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Alexandria Engineering Journal · 2024 · IF 6.2

Electrochemical detection of human papillomavirus DNA based on an ultrasensitive electrochemical sensing platform using N-graphene paper

Jia Wang,Juelan Ye,Gang Li

Human papillomavirus (HPV) is the primary cause of cervical cancer, a major global health concern affecting women worldwide. Early detection of high-risk HPV genotypes is crucial for timely intervention and reducing disease burden. However, current detection methods often lack sensitivity, speed, or cost-effectiveness, especially in resource-limited settings. This work addresses this critical need by developing an ultrasensitive electrochemical biosensing platform based on nitrogen-doped graphene paper electrodes for quantifying high-risk HPV16 DNA sequences. The N-graphene nanohybrid, fabricated via simple solvothermal treatment of biomass-derived graphene oxide, demonstrated significantly enhanced electrical and electrocatalytic properties compared to undoped graphene. DNA detection was achieved through characteristic oxidation signals of guanine bases, which displayed a wide linear dynamic range (0.5–100 μg/mL), low detection limit (75 pg/mL), and excellent reproducibility (relative standard deviation <3.5 %). Detailed spectroscopic and electrochemical analyses revealed the key roles of pyridinic nitrogen defects in improving interfacial charge transfer kinetics and mitigating biofouling issues. This synergistic combination of high electrical conductivity and versatile surface functionality paves the way for equipment-free, point-of-care genosensor devices tailored for quantitative biomarker screening in resource-constrained environments.

研究领域: 生物医学工程 · 电化学 · 分子生物学 · 癌症研究 · 纳米技术 · 即时诊断
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BIOSENSORS & BIOELECTRONICS · 2022 · IF 12.545

Nanozyme-strip for rapid and ultrasensitive nucleic acid detection of SARS-CoV-2

Xiangqin Meng,Sijia Zou,Dandan Li,Jiuyang He,Ling Fang,Haojue Wang,Xiyun Yan,Demin Duan,Lizeng Gao

The coronavirus disease 2019 (COVID-19) pandemic has created a huge demand for sensitive and rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The current gold standard for SARS-CoV-2 detection is reverse transcription-polymerase chain reaction (RT-PCR)-based nucleic acid amplification. However, RT-PCR is time consuming and requires specialists and large instruments that are unattainable for point-of-care testing (POCT). To develop POCT for SARS-CoV-2, we combined recombinase polymerase amplification (RPA) and FeS 2 nanozyme strips to achieve facile nucleic acid amplification and subsequent colorimetric signal enhancement based on the high peroxidase-like activity of the FeS 2 nanozymes. This method showed a nucleic acid limit of detection (LOD) for SARS-CoV-2 of 200 copies/mL, close to that of RT-PCR. The unique catalytic properties of the FeS 2 nanozymes enabled the nanozyme-strip to amplify colorimetric signals via the nontoxic 3,3′,5,5′-tetramethylbenzidine (TMB) substrate. Importantly, the detection of clinical samples of human papilloma virus type 16 (HPV-16) showed 100% agreement with previous RT-PCR results, highlighting the versatility and reliability of this method. Our findings suggest that nanozyme-based nucleic acid detection has great potential in the development of POCT diagnosis for COVID-19 and other viral infections.

研究领域: 分子生物学 · 病毒学 · 即时诊断 · 纳米技术
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