BIOMATERIALS
·
2022
·
IF 15.304
Liming Zhang,Kun Wang,Yuheng Huang,Hui Zhang,Long Zhou,Ang Li,Yunyan Sun
There is a lack of effective treatment methods for advanced cervical, and the therapeutic HPV vaccine is a promising option. The design of an efficient therapeutic vaccine is one of the main challenges. In the current study, we constructed a novel HPV nanovaccine that could effectively inhibit the progression of cervical cancer by combining nanotechnology and photodynamic therapy. This nanovaccine was constructed by linking bovine serum albumin (BSA) with the E7 antigen and then encapsulating the photosensitizer and adjuvant through disulfide bonds to form a highly biocompatible and stable structure. Due to its slow-release properties and targeted delivery to lymph nodes combined with infrared laser irradiation of photosensitizers to produce a photo-oxygen response, this vaccine could effectively induce the maturation of dendritic cells and stimulate T cell effects, thereby enhancing antitumor immunity. This prevention and treatment of tumors was experimentally demonstrated in a TC-1 cervical cancer model in C57BL/6 mice. This strategy can be applied to the design of therapeutic HPV vaccines in the future for clinical use.
研究领域:
肿瘤学
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免疫学
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纳米技术
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病毒学
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Yin Zhao,Dongjuan Chen,Zhichen Xu,Tao Li,Jiang Zhu,Rui Hu,Guoyong Xu,Ying Li,Yunhuang Yang,Maili Liu
Fast, simplified, and multiplexed detection of human papillomaviruses (HPVs) is of great importance for both clinical management and population screening. However, current HPV detection methods often require sophisticated instruments and laborious procedures to detect multiple targets. In this work, we developed a simple microfluidic dual-droplet device (M-D3) for the simultaneous detection of HPV16 and HPV18 by combining the CRISPR-Cas12a system and multiplexed recombinase polymerase amplification (RPA) assay. A new approach of combining pressure/vacuum was proposed for efficient droplet generation with minimal sample consumption. Two groups of droplets that separately encapsulate the relevant Cas12a/crRNA and the fluorescent green or red reporters are parallelly generated, followed by automatic imaging to discriminate the HPV subtypes based on the specific fluorescence of the droplets. The M-D3 platform performs with high sensitivity (∼0.02 nM for unamplified plasmids) and specificity in detecting HPV16 and HPV18 DNA. By combining the RPA and Cas12a assay, M-D3 allows on-chip detection of HPV16 and HPV18 DNA simultaneously within 30 min, reaching a detection limit of 10–18 M (∼1 copy/reaction). Moreover, the outstanding performance of M-D3 was validated in testing 20 clinical patient samples with HPV infection risk, showing a sensitivity of 92.3% and a specificity of 100%. By integrating the dual-droplet generator, CRISPR-Cas12a, and multiplexed RPA, the M-D3 platform provides an efficient way to discriminate the two most harmful HPV subtypes and holds great potential in the applications of multiplexed nucleic acid testing.
研究领域:
分子生物学
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医学检测
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生物技术
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2025
·
IF 2.6
Yan Tan,Zhipeng Wang,Haowen Yin,Peng Yu
The cervical cancer is the fourth most common cancer among women worldwide. Human papillomavirus type 16 (HPV16) is one of the common biomarkers which cause the cervical cancer. In this work, an electrochemical sensor based on a triblock polyadenine-based probe (TPP) and copper nanoclusters (CuNCs) was constructed for the rapid, sensitive and selective detection of HPV16. The TPP contained the central polyadenine (PolyA) segment and two flanking DNA probes. The middle PolyA segment had a high affinity to the gold electrode surface, leading to the adjustable density of the TPP by the length of PolyA. When the DNA template that mediated the formation of CuNCs was introduced, the DNA template partly hybridized with the two flanking DNA probes of the TPP. A large number of CuNCs were synthesized on the DNA template, producing a big electrochemical impedance signal. When the target DNA (HPV16) was present, it bound to the two flanking DNA probes of the TPP, which resulted in the release of the DNA template from the electrode and produced a small electrochemical impedance signal. The limit of detection (LOD) for the detection of HPV16 was 3.34 pM and the linear range was 10 pM - 10 μM. The designed sensor demonstrated good sensitivity, good selectivity, and satisfied recovery, providing the valuable insights in the cervical cancer prevention and the development of the electrochemical biosensors.
研究领域:
生物传感器
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纳米技术
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分子诊断学
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电化学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Qingxiang Wang,Min Liu,Jihong Zhao,Jiahao Yuan,Shasha Li,Ruijiang Liu
The prevention, diagnosis and treatment of cancer have always been the focus of medical research. In this study, a label-free, rapid, simple, sensitive, and specific method for the detection of HPV16 E7 oncoprotein was developed. The electrochemical biosensor platform was constructed by magnetic self-assembly of α-Fe 2 O 3 /Fe 3 O 4 @Au nanocomposites onto the surface of magnetic glass carbon electrode (MGCE), and the nanocomposite was connected to aptamer through Au S bond to construct a probe to capture HPV16 E7. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were applied to verify the performance of the constructed biosensor. The condition optimization and performance analysis were carried out by differential pulse voltammetry (DPV). Under optimal conditions, the biosensor exhibited a strong linearity between current value and the logarithm of HPV16 E7 oncoprotein concentration in the range of 10 pg/mL – 0.1 μg/mL, with a limit of detection (LOD) of 159 fg/mL and a limit of quantification (LOQ) of 530 fg/mL, and it also revealed excellent reproducibility, long-term stability, and anti-interference ability. In a word, the biosensor would contribute to the early diagnosis of oncoprotein HPV16 E7 and had promising application prospects.
研究领域:
医学诊断
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生物传感技术
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纳米材料科学
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产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2024
·
IF 2.7
Huanxin Xiao,Weiguang Chen,Mingxia Lin,Shilin Jiang,Xiping Cui,Suqing Zhao
Cervical cancer (CC) remains one of the most severe global health challenges affecting women, primarily due to persistent infection with high-risk human papillomavirus (HPV) subtypes, particularly with HPV16 and HPV 18. Effective detection of these high-risk HPV strains is crucial for CC prevention. Current screening programs for HPV DNA include PCR and in situ hybridization, which are accurate and sensitive. However, these approaches demand a high level of expertise, along with expensive instruments and consumables, thus hindering their widespread use. Therefore, there is a compelling demand to develop an efficient, straightforward, and cost-effective method. Herein, we propose a lateral flow immunoassay (LFIA) method based on Au@PdPt nanoparticles for the simultaneous detection and genotyping of HPV16 and HPV18 within 15 min. This innovative approach allows for qualitative assessment by the naked eye and enables semi-quantitative detection through a smartphone. In this study, under optimal conditions, the qualitative visual limits of detection (vLOD) for HPV16 and HPV18 reached 0.007 nM and 0.01 nM, respectively, which were 32-fold and 20-fold more sensitive than conventional AuNPs-LFIA for HPV16 and HPV18, respectively. Meanwhile, semi-quantitative limits of detection (qLOD) for HPV16 and HPV18 were 0.05 nM and 0.02 nM, respectively. In conclusion, our formulated approach represents a significant step forward in HPV detection and genotyping, with the potential to enhance accessibility and effectiveness in the early diagnosis of CC at the point of care and beyond.
研究领域:
医学诊断
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纳米技术
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癌症研究
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即时检测
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2022
·Vol. 147
·期 10
·2272-2279
·
IF 5.227
Tao Wen,Chenchen Xia,Qiubo Yu,Yujie Yu,Siyuan Li,Chunli Zhou,Kexin Sun,Song Yue
Cervical cancer is a common cancer in women. HPV16 E6 oncoprotein is a reliable biomarker for cervical cancer. Although there are other methods for detecting E6 oncoprotein, the electrochemical method has more advantages, such as low cost, convenience and speed. In this study, a novel dual-signal electrochemical immunosensor for quick and sensitive detection of E6 oncoprotein based on a high efficiency catalyst and signal label was developed. Herein, to achieve quick detection, palladium–boron–phosphorus dendritic ternary nanospheres (PdBP NSs) not only acted as a catalyst to catalyze H2O2, but also as a support material to capture antibodies. Moreover, to realize sensitive detection, nanocomposites of mesoporous silica nanoparticles loaded with methylene blue and coated with chitosan (MBSi-Chi) were synthesized as a signal label, which can produce electrochemical signal. Under optimal conditions, the label-free immunosensor exhibited a linear range of 100 fg mL−1 to 4 ng mL−1 with a detection limit of 72.8 fg mL−1 (S/N = 3), and the sandwich-type immunosensor presented a linear range of 50 fg mL−1 to 4 ng mL−1 with a detection limit of 34.1 fg mL−1 (S/N = 3). The as-prepared dual-signal immunosensor had desirable specificity, stability and repeatability, implying its potential applications in clinical laboratory.
研究领域:
生物化学
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纳米技术
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分析化学
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生物医学工程
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癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2023
·
IF 12.6
Hao Bai,Yuqing Liu,Linbo Gao,Tao Wang,Xiaoli Zhang,Jie Hu,Lisha Ding,Yueting Zhang,Qian Wang,Lei Wang,Jianlong Li,Zhifeng Zhang,Yang Wang,Chenlan Shen,Binwu Ying,Xiaoyu Niu,Wenchuang Hu
Screening for high-risk human papillomavirus (HPV) infection is one of the most important preventative measures for cervical cancer. However, fast, convenient, and low-cost HPV detection remains challenging, especially in resource-limited settings. Here, we report a portable all-in-one device (PAD) for point-of-care testing (POCT) for HPV16 and HPV18 DNA in cervical swabs. The PAD was engineered to integrate modules for extraction-free sample lysis, loop-mediated isothermal amplification (LAMP) with lyophilized reagent beads, and real-time colorimetric signal sensing into a single miniaturized device, considerably shortening the sample-to-result time to 15 min. The precision liquid handling in the completely sealed microfluidic chip is achieved by a uniquely designed pressure-balanced automatic liquid flow mechanism, thereby eliminating the need for manual manipulation of liquids and thus the risk of biohazards . The PAD employs an improved real-time colorimetric LAMP (rcLAMP) assay with a limit of detection (LOD) of 1 copy/μL, enabled by enhanced assay chemistry to maximize the reaction kinetics . To validate this device for clinical application, we tested 206 clinical cervical swab samples and obtained a sensitivity of 92.1% and a specificity of 99.0%. This custom PAD enabled by microfluidic and electronic engineering techniques can be configured for the simultaneous detection of HPV16 and HPV18 or other pathogens in point-of-care applications.
研究领域:
医疗设备
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分子生物学
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癌症研究
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即时诊断
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微流控技术
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产品关联
DOI
PubMed
高影响因子
Journal of Radiation Research and Applied Sciences
·
2024
·
IF 1.7
Zheng Feng,Zhouzhan Luo
This work aimed to evaluate the therapeutic efficacy of clustered regularly interspaced short palindromic repeats (CRISPR) ribonucleic acid (RNA) nanoparticles (NPs) in the therapy of cervical cancer (CC) using ultrasound elastography imaging. Using poly(β-amino esters) (PBAE), CRISPR RNA NPs encapsulating Human Papillomavirus 16 (HPV16) E7, namely Poly(β-amino ester) (PBAE)/CRISPR16E7-GFP and PBAE/shRNA-16E7, were prepared. The characterization of these NPs was conducted using transmission electron microscopy (TEM) and laser diffraction particle size analysis. The cytotoxicity of PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 NPs on CC cell lines SiHa, HeLa, and CaSki was assessed using the cell counting kit-8 (CCK-8) assay. Sixty female Sprague Dawley (SD) rats were rolled into six groups randomlyas follows: the blank Ctrl group (Group A, no treatment), the model group (Group B, CC model), the pSpCas9-GFP plasmid group (Group C, CC model + pSpCas9-GFP), the PBAE/CRISPR-16E7 group (Group D, CC model + PBAE/CRISPR-16E7), the pSIREN-U6-shRNA-CMV-iRFP plasmid group (Group E, CC model + pSIREN-U6-shRNA-CMV-iRFP), and the PBAE/shRNA-16E7 group (Group F, CC model + PBAE/shRNA-16E7), each consisting of 10 rats. The impact of NPs on the expression levels (ELs) of HPV16E7 and RB1 proteins in tumor tissues was assessed using Western Blot (WB) analysis. Additionally, ultrasound elastography imaging was employed to analyze the strain ratio (SR) and shear wave velocity (SWV) in lesions of various rat groups. The results indicated that the PBAE/CRISPR16E7-GFP NPs exhibited a particle size of 125.64 ± 7.8 nm, a zeta potential of 19.17 ± 3.61 mV, and a polydispersity index (PDI) of 0.281 ± 0.03. These NPs demonstrated a regular spherical structure with a compact morphology. The PBAE/shRNA-16E7 NPs displayed a particle size of 112.93 ± 9.1 nm, a zeta potential of 13.54 ± 1.39 mV, and a PDI of 0.185 ± 0.03. They exhibited a uniform distribution of spherical shape with regularity in size. The plasmids within PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 NPs exhibited distinct trends of burst and sustained release. The viability of SiHa, HeLa, and CaSki cells remained unaffected by PBAE/CRISPR16E7-GFP NPs. At various mass ratios, neglectable differences ( P > 0.05) were observed in cell viability of SiHa, HeLa, and CaSki cells treated with PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 NPs relative to Ctrl group. Relative to Group B, both Groups C and E exhibited a drastic decrease in tumor volume, tumor mass, and HPV16E7 protein ELs ( P < 0.05), whereas Groups D and F showed a notably greater reduction in tumor volume, tumor mass, and HPV16E7 protein ELs ( P < 0.01). The HPV16E7 protein ELs, SR, and SWV values greatly increased ( P < 0.001) in tumors of Group B rats while the EL of RB1 protein notably decreased ( P < 0.001) versus Group A. Groups C and E demonstrated elevated HPV16E7 ELs, SR, and SWV values ( P < 0.05), with a marked decrease in RB1 protein EL ( P < 0.001). Group F exhibited a notable reduction in HPV16E7 protein levels, SR, and SWV values ( P < 0.001).The CRISPRRNA NPs composed of PBAE encapsulating HPV16 E7, namely PBAE/CRISPR16E7-GFP and PBAE/shRNA-16E7 plasmids, demonstrated a significant role in CC therapy. These NPs hold potential application value in the treatment of HPV-related CC, indicating their importance in addressing this particular disease.
研究领域:
分子生物学
·
肿瘤学
·
医学影像学
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产品关联
DOI
高影响因子
BIOCHEMICAL GENETICS
·
2025
·
IF 1.6
Yang Min,Ma Yuejiang,Cao Zhu,Zhan Hong,Jin Ye,Huang Xiufeng,Yang Shizhou
Cervical cancer (CC) is one of the most prevalent cancers among women globally. The primary cause of CC is persistent infection with high-risk types of human papillomavirus (HPV), particularly HPV16, whose E7 oncoprotein plays a pivotal role in carcinogenesis and the maintenance of stem cell-like characteristics. RTKN2 participates in the progression of various cancers. However, the precise functions of RTKN2 in regulating CC remain unclear. The effects of HPV16 E7 in CC cells were evaluated using MTT, western blotting, Transwell, and sphere formation assays. Transcriptome sequencing and bioinformatics analyses were used to identify the targets of HPV16 E7. The expression levels of the target (RTKN2) in clinical samples were assessed using immunohistochemistry (IHC). The function and mechanism of RTKN2 in CC cells were investigated by the knockdown and overexpression approaches, as well as dual-luciferase reporter assay. HPV16 E7 exhibited a positive correlation on the malignant phenotype and stemness of CC cells. RTKN2 was identified as a target of HPV16 E7, and a reduction in its expression levels was caused by knockdown of HPV16 E7. The high expression of RTKN2 was associated with a poor prognosis in CC. HPV16 E7 may regulate RTKN2 expression by modulating the binding activity of E2F1 to the RTKN2 promoter. Upregulated RTKN2 activates the NF-κB signaling pathway, enhances the stemness of CC cells, and ultimately promotes malignant progression.
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Yan Tan,Zhipeng Wang,Peng Yu
Human papillomavirus type 16 (HPV16) is a significant biomarker for cervical cancer, and its precise detection is vital for diagnosing the disease. The work involved developing an electrochemical sensor by utilizing copper nanoclusters (CuNCs), which integrated triblock polyadenine probe (TPP) and hybridization chain reaction (HCR) for sensitively detecting HPV16 DNA. The TPP was assembled on the electrode owing to the strong affinity between its adenine bases and gold. The absence of HPV16 DNA allowed the capture probe to bind with the hairpin DNA, which triggered HCR and generated a large number of CuNCs, causing a substantial electrochemical impedance signal. However, when there was HPV16 DNA in the reaction system, it could bind specifically to the two flanking probes of TPP, causing the release of the capture probe. Without capture probe, the HCR was unable to be triggered, thus generating a small amount of CuNCs and resulting in a reduced electrochemical impedance signal. With the optimal conditions, the sensor could detect HPV16 DNA within a broad linear range of 1 × 10 −12 M – 1 × 10 −5 M and had a low detection limit of 2.6 × 10 −13 M. A new analytical platform for the sensitive detection of DNA was developed, which exhibited good sensitivity and selectivity.
研究领域:
生物分析化学
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生物传感器与生物电子学
·
分子诊断
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纳米生物技术
·
癌症标志物
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产品关联
DOI
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2024
·
IF 9.4
Mingxia Lin,Huiyi Yang,Qinglan Li,Huanxin Xiao,Shilin Jiang,Jinhui Liang,Xiping Cui,Suqing Zhao
Cervical cancer is one of the most common gynecological malignancies, with the vast majority of which being caused by persistent infection with Human Papillomavirus (HPV) 16 and 18. The current available HPV detection methods are sensitive and genotyped but are restricted by expensive instruments and skilled personnel. The development of an easy-to-use, rapid, and cost-friendly analysis method for HPV is of great need. Herein, hollow palladium-ruthenium nanocages modified with two oligonucleotides (PdRu capture probes) were constructed for genotyping and simultaneous detection of target nucleic acids HPV16 and HPV18 by dual lateral flow assay (DLFA). PdRu capture probes were endowed with bi-functions for the first time, which could be used to output signals and hybridize target nucleic acids . Under optimized conditions, the PdRu based-DLFA with detection limits of 0.93 nM and 0.19 nM, respectively, exhibited convenient operation, and high sensitivity. Meanwhile, the DLFA achieved excellent rapid detection within 20 min, which was attributed to capture probes that can be directly bound to amplification-free target nucleic acids . Therefore, the development of PdRu-based DLFA can be utilized for rapid, sensitive, and simultaneous genotyping detection of HPV16 and HPV18, showing great application for nucleic acid detection .
研究领域:
医学诊断
·
纳米技术
·
分子生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
Aggregate
·
2024
·
IF 13.9
Yi Long,Shurui Tao,Dongni Shi,Xingyu Jiang,Tian Yu,Yingxi Long,Libing Song,Guozhen Liu
Developing the sensitive point-of-care testing (POCT) of oncogenic nucleic acids from human papillomavirus (HPV) infection is essential in preventing cervical cancer, especially in resource-limited settings. Rolling circle amplification (RCA) is attractive in achieving POCT via nucleic acid-based aggregation under isothermal conditions. However, the influence of RCA product structure on the aggregation remains unexplored resulting in limited sensitivity. Here, a minimum secondary structured RCA technique (MSS-RCA) is developed by designing a unique circular template, demonstrating significantly enhanced detection sensitivity with only one amplification step and one primer under isothermal conditions. The amplification efficiency of MSS-RCA could be kinetically manipulated by controlling the secondary structure of the circular template. Introducing the invertase probe to MSS-RCA, HPV16 E6/E7 nucleic acid target was detected with a personal glucose meter (PGM) with a sensitivity of 5 f m (50 zmol in 10 µL). This integrated MSS-RCA-PGM detection system was successfully applied to detect HPV16 E6/E7 mRNA extracted from 54 cervical swab samples reaching a positive predictive value of 100.00% and negative predictive values of 96.00% (77.77% to 99.40%, 95% CI). MSS-RCA-PGM provides a sensitive POCT platform for the detection of nucleic acid biomarkers for screening of cervical cancer or other diseases.
研究领域:
分子生物学
·
癌症筛查
·
即时诊断
·
核酸扩增
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）