SENSORS
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2023
·Vol. 23
·期 17
·7380
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IF 3.9
Yuxing Yang,Yazhen Liao,Yang Qing,Haiyu Li,Jie Du
Cervical cancer is an important topic in the study of global health issues, ranking fourth among women’s cancer cases in the world. It is one of the nine major cancers that China is focusing on preventing and treating, and it is the only cancer that can be prevented through vaccination. Systematic and effective screening for human papilloma (HPV) infection, which is closely linked to the development of cervical cancer, can reduce cervical cancer incidence and mortality. In this paper, an electrochemical sensor was designed to detect HPV 16 using dual-signal amplification. An APTES-modified glassy carbon electrode was used for improved stability. Gold nanoparticles and a chain amplification reaction were combined for signal amplification. The limit of detection (LOD) of this electrochemical sensor was 1.731 × 10−16mol/L, and the linear response of the target detector range was from 1.0 × 10−13mol/L to 1.0 × 10−5mol/L (R2= 0.99232). The test of serum sample recovery showed that it has good anti-interference, and the performance of all aspects was improved to different degrees compared with the previous research from the team. The designed sensor is centered around the principles of low cost, high sensitivity and stability, which provides new ideas for the future development of cervical cancer prevention and electrochemical biosensors.Keywords:electrochemical biosensor;high-risk human papillomavirus;gold nanoparticles;3-Aminopropyltriethoxysilane
研究领域:
生物医学工程
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分析化学
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分子生物学
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癌症研究
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PubMed
高影响因子
International Journal of Nanomedicine
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2021
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IF 6.4
Jinfeng Xiong,Songwei Tan,Long Yu,Hui Shen,Shen Qu,Chong Zhang,Ci Ren,Da Zhu,Hui Wang
Introduction Persistent HR-HPV (high-risk human papillomavirus) infection is the main cause of cervical cancer. The HPV oncogene E7 plays a key role in HPV tumorigenesis. At present, HPV preventive vaccines are not effective for patients who already have a cervical disease, and implementation of the recommended regular cervical screening is difficult in countries and regions lacking medical resources. Therefore, patients need medications to treat existing HPV infections and thus block the progression of cervical disease. Methods In this study, we developed nanoparticles (NPs) composed of the non-viral vector PBAE546 and a CRISPR/Cas9 recombinant plasmid targeting HPV16 E7 as a vaginal treatment for HPV infection and related cervical malignancies. Results Our NPs showed low toxicity and high biological safety both in vitro (cell line viability) and in vivo (various important organs of mice). Our NPs significantly inhibited the growth of xenograft tumors derived from cervical cancer cell lines in nude mice and significantly reversed the cervical epithelial malignant phenotype of HPV16 transgenic mice. Conclusion Our NPs have great potential to be developed as a drug for the treatment of HPV-related cervical cancer and precancerous lesions.
研究领域:
肿瘤学
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分子生物学
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药学
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生物技术
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癌症治疗
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PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Xiong Jinfeng,Li Guannan,Mei Xinyu,Ding Jiahui,Shen Hui,Zhu Da,Wang Hui
The p53 gene has the highest mutation frequency in tumors, and its inactivation can lead to malignant transformation, such as cell cycle arrest and apoptotic inhibition. Persistent high-risk human papillomavirus (HR-HPV) infection is the leading cause of cervical cancer. P53 was inactivated by HPV oncoprotein E6, promoting abnormal cell proliferation and carcinogenesis. To study the treatment of cervical intraepithelial neoplasia (CIN) and cervical cancer by restoring p53 expression and inactivating HPV oncoprotein, and to verify the effectiveness of nano drugs based on nucleic acid delivery in cancer treatment, we developed poly (beta-amino ester)537, to form biocompatible and degradable nanoparticles with plasmids (expressing p53 and targeting E7). In vitro and in vivo experiments show that nanoparticles have low toxicity and high transfection efficiency. Nanoparticles inhibited the growth of xenograft tumors and successfully reversed HPV transgenic mice’s cervical intraepithelial neoplasia. Our work suggests that the restoration of p53 expression and the inactivation of HPV16 E7 are essential for blocking the development of cervical cancer. This study provides new insights into the precise treatment of HPV-related cervical lesions.
研究领域:
肿瘤学
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分子生物学
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纳米技术
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基因治疗
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癌症研究
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2020
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IF 7.727
Xueqin Gao,Zhuang Jin,Xiangyu Tan,Chong Zhang,Chenming Zou,Wei Zhang,Jiahui Ding,Bhudev C. Das,Konstantin Severinov,Inga Isabel Hitzeroth,Priya Ranjan Debata,Dan He,Xin Ma,Xun Tian,Qinglei Gao,Jun Wu,Rui Tian,Zifeng Cui,Weiwen Fan,Zhaoyue Huang,Chen Cao,Yuxian Bao,Songwei Tan,Zheng Hu
Persistent high-risk HPV infection is the main factor for cervical cancer . HPV E7 oncogene plays an important role in HPV carcinogenesis. Down-regulation of E7 oncogene expression could induce growth inhibition in HPV-positive cells and thus treats HPV related cervical cancer. Here we developed a non-virus gene vector based on poly(amide-amine)-poly(β-amino ester) hyperbranched copolymer (hPPC) for the delivery of CRISPR/Cas9 system to specifically cleave HPV E7 oncogene in HPV-positive cervical cancer cells. The diameter of polyplex nanoparticles (NPs) formed by hPPCs/linear poly(β-amino ester) (PBAE) and plasmids were approximately 300 nm . These hPPCs/PBAE-green fluorescence protein plasmids polyplex NPs showed high transfection efficiency and low toxicity in cells and mouse organs. By cleaving HPV16 E7 oncogene, reducing the expression of HPV16 E7 protein and increasing intracellular retinoblastoma 1 (RB1) amount, hPPCs/PBAE-CRISPR/Cas9 therapeutic plasmids polyplex NPs, especially highly branched hPPC1-plasmids polyplex NPs, exhibited strong growth inhibition of cervical cancer cells in vitro and xenograft tumors in nude mice . Together, the hPPCs/PBAE polyplex NPs to deliver HPV16 E7 targeted CRISPR/Cas9 system in this study could potentially be applied to treat HPV-related cervical cancer.
研究领域:
癌症研究
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基因治疗
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纳米技术
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分子生物学
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PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2024
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IF 5.4
Jingyuan Ji,Chenjia Zhao,Chen Hua,Lu Lu,Yuan Pang,Wei Sun
As attempting personalized medicine, 3D-printed tissue engineering scaffolds are employed to combine with therapeutic proteins/peptides especially in the clinical treatment of infectious diseases, genetic diseases, and cancers. However, current drug-loading methods, such as immersion and encapsulation, usually lead to the burst release of the drugs. To address these issues, we proposed an integrated strategy toward the long-term controlled release of protein. In this study, patient-customized 3D scaffolds incorporated with drug-loaded microspheres were printed to realize the effective delivery of the anti-human papillomavirus (anti-HPV) protein after cervical conization in the treatment of cervical cancer. The 3D-printed scaffold could provide mechanical support to the defect site and ensure local release of the drug to avoid systemic administration. Meanwhile, microspheres serve as functional components to prevent the inactivation of proteins, as well as regulate their release period to meet the time requirement of different treatment courses. The research also utilized bovine serum albumin as a model protein to validate the feasibility of these scaffolds as a generic technology platform. The bioactivity of the released anti-HPV protein was validated using a pseudovirus model, which demonstrated that the microsphere encapsulation would not cause protein denaturation during the scaffold fabrication process. Besides, 3D-printed scaffolds incorporated with carboxylated chitosan microspheres were biocompatible and beneficial for cell attachment, which have been demonstrated by favorable cell viability and better coverage results for HeLa and HFF-1. This study highlights the great potential of scaffolds incorporated with microspheres to serve as tissue engineering candidate products with the function of effective protein delivery in a long-term controlled manner and personalized shapes for clinical trials.
研究领域:
生物医学工程
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药学
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组织工程
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癌症研究
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药物递送系统
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个性化医疗
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高影响因子
BIOSENSORS & BIOELECTRONICS
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2021
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IF 10.618
Peng-Fei Liu,Kai-Ren Zhao,Zhi-Jun Liu,Li Wang,Shu-Ying Ye,Guo-Xi Liang
CRISPR/Cas system have drawn increasing attention in accurate and sensitive nucleic acids detection. Herein, we reported a novel Cas12a-based electrochemiluminescence biosensor for target amplification-free human papilloma virus subtype (HPV-16) DNA detection. During this detection process, Cas12a employed its two-part recognition mechanism to improve the specificity and trans-cleavage capability to achieve signal amplification , while L-Methionine stabilized gold nanoclusters (Met-AuNCs) were served as high-efficiency ECL emitters to achieve ECL signal transition. Given the unique combination of Cas12a with ECL technique, the detection limit was determined as 0.48 pM and the whole detection could be completed within 70 min. We also validated the practical application of the proposed biosensor by using undiluted human blood samples, which gives impetus to the design of new generations of CRISPR/Cas detection system beyond the traditional ones with ultimate applications in sensing analysis and diagnostic technologies.
研究领域:
生物技术
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医学诊断
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DOI
PubMed
高影响因子
TALANTA
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2024
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IF 5.6
Jiajia Hu,Yang Yu,Xiaoyan Pan,Yue han,Xinyi She,Xiaojun Liu,Qingquan Zhang,Hongwei Gai,Chenghua Zong
Human papillomavirus (HPV) is a prevalent sexually transmitted pathogen associated with cervical cancer . Detecting high-risk HPV (hr-HPV) infections is crucial for cervical cancer prevention, particularly in resource-limited settings. Here, we present a highly sensitive and specific sensor for HPV-16 detection based on CRISPR/Cas12a coupled with enhanced single nanoparticle dark-field microscopy (DFM) imaging techniques . Ag–Au satellites were assembled through the hybridization of AgNPs-based spherical nucleic acid (Ag-SNA) and AuNPs-based spherical nucleic acid (Au-SNA), and their disassembly upon target-mediated cleavage by the Cas12a protein was monitored using DFM for HPV-16 quantification. To enhance the cleavage efficiency and detection sensitivity, the composition of the ssDNA sequences on Ag-SNA and Au-SNA was optimized. Additionally, we explored using the SynSed technique (synergistic sedimentation of Brownian motion suppression and dehydration transfer) as an alternative particle transfer method in DFM imaging to traditional electrostatic deposition. This addresses the issue of inconsistent deposition efficiency of Ag–Au satellites and their disassembly due to their size and charge differences. The sensor achieved a remarkable limit of detection (LOD) of 10 fM, lowered by 9-fold compared to traditional electrostatic deposition methods . Clinical testing in DNA extractions from 10 human cervical swabs demonstrated significant response differences between the positive and negative samples. Our sensor offers a promising solution for sensitive and specific HPV-16 detection, with implications for cancer screening and management.
研究领域:
分子生物学
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医学诊断
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纳米技术
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2025
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IF 13.2
Hongkai Wang,Yinzheng Niu,Hui Liu,Ye Zhu
Nucleic acid detection is crucial for early disease diagnosis and related clinical applications. Exploring nucleic acid amplification-free yet highly sensitive detection strategies is of significance for the development of accurate and user-friendly point-of-care testing devices. Herein, a modularized universal electrochemical sensing strategy was proposed based on the synergistic effect of CRISPR/Cas12 system and nanoporous materials. The trans -cleavage activity of Cas12a, which was activated by HPV-16 target, was utilized to cut the gatekeepers of mesoporous silica nanoparticle nanocontainers. The released methylene blue was entrapped by a mercaptobenzoic acid functionalized nanoporous gold (NPG) sensing platform. By virtue of the excellent electrocatalytic ability of NPG, ultrasensitive detection of HPV-16 was achieved over a broad linear range of 7 orders of magnitude with a detection limit as low as 0.41 fM. Moreover, determination of HPV-18 was easily achieved by only altering crRNA, revealing the remarkable universality of this strategy and its superiority of modularized design. The practical applicability of the proposed sensing strategy was verified in terms of specificity, stability, and complex biological sample analysis, demonstrating its promising prospects in the development of reliable, universal, robust, and user-friendly point-of-care diagnostic devices.
研究领域:
生物技术
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医学诊断
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纳米科学
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DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2022
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IF 9.221
Ailing Su,Yuan Liu,Xiumian Cao,Weiqing Xu,Chongyang Liang,Shuping Xu
A new gene detection platform based on surface-enhanced Raman spectroscopy (SERS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas12a system is developed, which is applied for virus gene detections. CRISPR/Cas12a activated by CRISPR ribonucleic acid (crRNA) can recognize and lock the complementary target double-stranded deoxyribonucleic acid (dsDNA), followed by the cis -cleavage on the dsDNA and the trans -cleavage on the nearby linker single-stranded DNA (ssDNA). Target-induced trans -ssDNA cleavage leads to a failure in an aggregation behavior of the designed SERS probe pair that was bridged by the linker ssDNA, which causes the SERS intensity reduced relative to the control trial that gives much stronger SERS due to the severe aggregation state of SERS probes caused by intact linker ssDNA. This sensing method achieves the highly sensitive detections of human papillomavirus (HPV) genes in serum and pseudovirus within 40 min. The detection sensitivity of this CRISPR/Cas-SERS platform can reach pM. Owing to the flexible designs of the DNA probe and crRNA, this CRISPR/Cas-SERS sensing system is a universal gene detection tool, which can be applied for the in-vitro diagnosis field and point-of-care testing.
研究领域:
分子生物学
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医学诊断
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生物传感技术
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Xiangyan Chen,Guiyuan Zhao,Xiaohan Yang,Fei Liu,Shixin Wang,Xia Zhao
Sexually transmitted diseases (STDs) are usually caused by co-infections of bacteria and viruses. However, there is a lack of products that possess both antibacterial and antiviral activities without using chemical drugs. Here, we developed a carrageenan silver nanoparticle composite hydrogel (IC-AgNPs-Gel) based on the antiviral activity of iota carrageenan (IC) and the antibacterial effect of silver nanoparticles (AgNPs) to prevent STDs. IC-AgNPs-Gel showed excellent biocompatibility, hemostasis , antibacterial and antiviral effects. IC-AgNPs-Gel not only effectively prevented S. aureus , E. coli , P. aeruginosa , and C. albicans without using antibiotics, but also significantly inhibited human papilloma virus (HPV)-16 and HPV-6 without using chemotherapy drugs. Moreover, IC-AgNPs-Gel showed the effects of accelerating infected wound healing and reducing inflammation in a rat wound model infected with S. aureus . Therefore, the multifunctional hydrogel shows great potential application prospect in preventing STDs.
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高影响因子
Nature Communications
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2022
·Vol. 13
·期 1
·1-14
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IF 17.694
Xu Zhichen,Chen Dongjuan,Li Tao,Yan Jiayu,Zhu Jiang,He Ting,Hu Rui,Li Ying,Yang Yunhuang,Liu Maili
Fast, inexpensive, and multiplexed detection of multiple nucleic acids is of great importance to human health, yet it still represents a significant challenge. Herein, we propose a nucleic acid testing platform, named MiCaR, which couples a mi crofluidic device with CRISPR- C as12a a nd multiplex r ecombinase polymerase amplification. With only one fluorescence probe, MiCaR can simultaneously test up to 30 nucleic acid targets through microfluidic space coding. The detection limit achieves 0.26 attomole, and the multiplexed assay takes only 40 min. We demonstrate the utility of MiCaR by efficiently detecting the nine HPV subtypes targeted by the 9-valent HPV vaccine, showing a sensitivity of 97.8% and specificity of 98.1% in the testing of 100 patient samples at risk for HPV infection. Additionally, we also show the generalizability of our approach by successfully testing eight of the most clinically relevant respiratory viruses. We anticipate this effective, undecorated and versatile platform to be widely used in multiplexed nucleic acid detection.
研究领域:
生物技术
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分子生物学
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医学诊断
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PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2022
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IF 8.008
Yilei Lu,Xiujun Rong,Peng Wu,Jian Shou,Long Chen,Fang Luo,Cuiying Lin,Jian Wang,Bin Qiu,Zhenyu Lin
The discrepancy of the electrostatic interaction of negatively charged signal molecules to long and short DNA strands of the modified electrode surface has been used for the first time to the develop an electrochemiluminescence (ECL) biosensor for human papillomavirus 16 (HPV 16) DNA detection. The short single-stranded capture probe (CP) was modified first on the surface of the gold electrode, which only has a small amount of negative charge. The electrostatic interaction between the negatively charged tris(2,2′-bipyridyl) ruthenium(II) chloride hexahydrate-doped SiO2 nanoparticles (Ru@SiO2 NPs) and CP is weak, hence Ru@SiO2 NPs easily diffuse to the surface of the electrode to generate a strong ECL signal. Hybrid chain reaction (HCR) amplification products (long strand dsDNA) were prepared in homogeneous solution in advance. When the target was present, the dsDNA can be connected on the electrode surface and cause the enhancement of the negative charge on the electrode surface. Owing to electrostatic interaction and steric hindrance, Ru@SiO2 NPs are difficult to diffuse to the electrode surface, resulting in a significantly reduced ECL signal. The decrease of ECL signal is linearly correlated with the logarithm of the HPV concentration under optimal conditions, with the detection range being 0.1 fM −5 pM with a limit of 1.41 aM. This innovative methodology expands the application of electrostatic interaction in ECL sensing, but can also easily develop biosensors for detecting other targets by changing the DNA sequence used in this strategy.
研究领域:
生物医学工程
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分析化学
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PubMed
高影响因子
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