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
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
Journal of Radiation Research and Applied Sciences
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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
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肿瘤学
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医学影像学
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产品关联
DOI
高影响因子
BIOCHEMICAL GENETICS
·
2025
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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
Biosensors-Basel
·
2024
·Vol. 14
·期 12
·618
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IF 4.9
Shurui Tao,Yi Long,Guozhen Liu
The Phi29 DNA polymerase is renowned for its processivity in synthesizing single-stranded DNA amplicons by rolling around a circularized DNA template. However, DNA synthesis rolling circle amplification (RCA) is significantly hindered by the secondary structure in the circular template. To overcome this limitation, an engineered circular template without secondary structure could be utilized to improve the sensitivity of RCA-based assays without increasing its complexity. We herein proposed an entropy-driven special RCA technology for the detection of HPV16 E7 gene at room temperature. The strategy is composed of a molecular beacon containing a loop region for nucleic acid target recognition and a stem region to initiate RCA. With the target analyte, the stem region of the molecular beacon will be exposed and then hybridized with a special circular template to initiate the DNA amplification. We tested different designs of the molecular beacon sequence and optimized the assay’s working conditions. The assay achieved a sensitivity of 1 pM in 40 min at room temperature. The sensitivity of this assay, at 1 pm, is about a hundred-fold greater than that of conventional linear RCA performed in solution. Our proposed sensor can be easily reprogrammed for detecting various nucleic acid markers by altering the molecular beacon’s loop. Its simplicity, rapid assay time, and low cost make it superior to RCA sensors that utilize similar strategies.
研究领域:
分子生物学
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生物技术
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纳米技术
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分析化学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2021
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IF 10.618
Guolin Hong,Zhiyan Zou,Zhongnan Huang,Haohua Deng,Wei Chen,Huaping Peng
Persistent high-risk human papillomavirus (HPV) infection is the leading cause of cervical cancer. Efficient detection of HPV16 E7 is necessary for early diagnosis and cure of the disease. Here, a novel and high-performance Au nanocluster (AuNC) probe-based split-type electrochemiluminescent (ECL) assay platform has been established to detect these oncogenes , in which the nucleic acid hybridization assay and the ECL measurements are performed independently. The proposed approach combines superior magnetic nanobead enrichment and separation technology, specific nucleic acid hybridization technology, and high-efficiency AuNC probe ECL strategy, and shows excellent advantages. First, the split-type ECL sensing platform can effectively avoid interference from biological samples and adequately uses the ECL efficiency of the AuNC probe. Furthermore, the ultrahigh sensitivity assay of HPV DNA can be achieved without any complex nucleic acid amplification technique. Taking advantage of the above merits of split-type detection, the ECL DNA sensor achieved ideal low detection of 6.8 aM and a wide dynamic range bridging 10 orders of magnitude HPV16 E7. Furthermore, together with its favorable and powerful specificity, high sensitivity, and good selectivity , this strategy could detect HPV16 E7 DNA in human samples, which showed great consistency with the FDA-approved approach (Hybrid capture 2, HC2). Therefore, this work proposes a facile and reliable split-type ECL platform for HPV diagnosis and shows great potential for the early diagnosis of other diseases.
研究领域:
生物医学工程
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分子生物学
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分析化学
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纳米技术
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癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOMACROMOLECULES
·
2025
·
IF 5.4
Qianru Li,Yuhe Zhu,Jiahui Ding,Weizhen Pan,Yuwei Hu,Jiao Lu,Sihai Gao,Hongyang Jiang,Zhongyuan Yin,Songwei Tan
Gene therapy is often limited by gene vectors. To reduce the impact of intracellular reactive oxygen species and improve transfection efficiency, thioether bonds were introduced in poly(β-amino ester) (PBAE), a well-known nonviral gene vector, to synthesize PBAE-poly(β-thioether ester) copolymer (PBAE-TE). By varying the monomer feeding ratio and reaction time, the optimized copolymer (PBAE-TE2–5) showed the highest transfection efficiency in SiHa and HeLa cells (75.00 and 78.70%) with a 75:1 copolymer/GFP ratio. PBAE-TE2–5 also demonstrated superior transfection performance compared to PBAE in multiple cell lines (HeLa, Me180, C666–1, and HEK 293T) and better penetration capability in 3D spheroid cell models (SiHa and HEK 293T). The PBAE-TE2–5-CRISPR/Cas9 plasmid polyplexes could effectively edit target genes in HEK 293T (MUC2) and SiHa (HPV16 E7) cells, and inhibit cancer cell proliferation both in vitro and in vivo. These findings highlight the promising potential of PBAE-TE as an effective gene delivery system.
研究领域:
生物材料
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基因治疗
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高分子化学
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生物医学工程
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分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）