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
·
免疫学
·
纳米技术
·
病毒学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2016
·
IF 3.42
Qian Li,Dongming Xing,Lie Ma,Changyou Gao
As the most promising stem cell, bone marrow-derived mesenchymal stem cells (BMSCs) has attracted many attentions and applied widely in regenerative medicine. A biodegradable polyester with tunable affinity to BMSCs plays critical role in determining the properties of the BMSCs-based constructs. In this study, maleimide functionalized biodegradable polyester (P(MTMC-LA)) was synthesized through ring-opening copolymerization between l -lactide (LA) and furan-maleimide functionalized trimethylene carbonate (FMTMC) and a subsequent retro Diels-Alder reaction. P(MTMC-LA) was modified by different amounts of BMSCs specific affinity peptide (EPLQLKM, E7) through click-chemistry to investigate the effect on BMSCs. The E7 peptide modified P(MTMC-LA) was casted into films on glass slides and BMSCs were seeded onto the films. In vitro study showed that E7 peptide modified P(MTMC-LA) films supported BMSCs adhesion and proliferation compared to unmodified P(MTMC-LA) film. Besides, the adhesion and proliferation were enhanced by the increasing peptide grafting ratio. These results indicated that the novel biodegradable polyester can serve as a biomaterial with great potential application in tissue engineering and regenerative medicine.
研究领域:
生物材料学
·
再生医学
·
组织工程
✓ 已验证
DOI
PubMed
高影响因子
Stem Cell Research & Therapy
·
2025
·Vol. 16
·期 1
·1-16
·
IF 7.3
Chen Guangzi,Xu Tao,Gao Ran,Liu Wenbin,Li Weigang,Zeng Delu,Li Jian,Fang Xuan,Sheng Gaohong,Zhao Hongqi,Liu Chaoxu
Background Periosteum plays an important role in bone defect repair due to its rich vascular network and cells. However, natural periosteum is difficult to meet clinical requirements due to its low availability. Therefore, it is necessary to develop a tissue engineering strategy of biomimetic periosteum for bone defect repair. Methods Poly-ε-caprolactone/chitosan/Whitlockite electrospun bionic membrane (PCL/CS/WH) was prepared using electrospinning technology, then it was conjugated with an E7 peptide as PCL/CS/WH/E7 bionic membrane. The physical properties of the membranes were evaluated by TEM, FTIR and tensile strength testing. In vitro, LIVE/DEAD staining and Cell Counting Kit-8 assay of bone marrow mesenchymal stem cells (BMSCs) and Endothelial progenitor cells (EPCs) are used to assess the biocompatibility of bionic membranes. Matrigel was applied to evaluate the ability of the different composite nanofibers samples to promote angiogenesis. Mineralized nodule and collagen formation in the BMSCs was detected by alizarin red staining and sirius red staining respectively. The expression of osteogenesis related genes and angiogenesis associated genes were detected using quantitative real-time polymerase chain reaction (qRT-PCR). In vivo, the ability of PCL/CS/WH/E7 membrane to promote bone regeneration and angiogenesis was assessed by Micro-CT and associated staining. Result The addition of chitosan (CS) and E7 peptide (E7) enhanced the hydrophilicity and cytocompatibility of pure PCL membranes. Additionally, CS, E7 and Mg 2+ released from Whitlockite (WH) had a synergistic effect to promote angiogenesis and osteogenic differentiation. Three weeks after implantation, the membrane successfully bridged the bone defect and significantly promoted the formation of new bone and blood vessels. Conclusion The PCL/CS/WH/E7 membrane to achieve efficient repair of bone tissue and enriches clinical solutions for the treatment of critical bone defects.
研究领域:
组织工程
·
生物材料科学
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC BIOTECHNOLOGY
·
2025
·Vol. 25
·期 1
·1-20
·
IF 3.4
Long Shengyu,Wang Wentong,Chen Yongcheng,Wang Zhihua,Duan Hao,Yuan Ping,Xu Yunrong,Li Denghui,Zhang Wan,Wang Weizhou,He Fei
Background The repair of bone defects remains a significant clinical challenge. Although magnesium (Mg)-based biomimetic scaffolds are widely utilized for bone defect repair, the release of Mg²⁺ ions often leads to an alkaline microenvironment, thereby adversely affecting bone regeneration. Regenerative medicine strategies that leverage the recruitment of endogenous bone marrow mesenchymal stem cells (BMSCs) offer a novel approach to treating bone defects.Methods In this study, we employed poly(L-lactic acid) (PLLA) and polyethylene glycol (PEG) as shell materials and nanomagnesium oxide (nMgO) combined with gelatin (G) as core materials to fabricate coaxial fibre membranes with a “core‒shell” structure via coaxial electrospinning technology. Additionally, we grafted the BMSC-affinitive peptide E7 (EPLQLKM) onto the fibres to achieve specific recruitment of endogenous BMSCs.Results Morphological and structural analyses confirmed the successful formation of the “core‒shell” structure of the fibre membranes. Grafting E7 peptides enhanced the hydrophilicity and mechanical properties of the fibre membranes and maintained pH stability in vitro. In vitro experiments demonstrated that the functionalized fibre membranes significantly promoted BMSC proliferation, migration, and osteogenic differentiation. When implanted into a rat cranial defect model, we observed the formation of new bone tissue and the repair of the bone defect.Conclusion sE7 peptide-functionalized coaxial fibre membranes effectively facilitated bone defect repair by promoting the recruitment and osteogenic differentiation of BMSCs, demonstrating substantial potential for tissue engineering applications.
研究领域:
生物医学工程
·
组织工程
·
干细胞生物学
·
材料科学与医学应用
·
骨科再生医学
✓ 已验证
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
·
生物传感技术
·
纳米材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Qihong Li,Chen Li,Jun Yan,Chunli Zhang,Yu Jiang,Xiantong Hu,Liwei Han,Li Li,Peng Wang,Lingzhou Zhao,Yantao Zhao
Repairing large bone defects remains a significant clinical challenge. Stem cell is of great importance in bone regeneration, and periosteum is rich in periosteal stem cell, which has a great influence on repairing bone defects. Bioengineered periosteum with excellent biocompatibility and stem cell homing capabilities to promote bone regeneration is of great clinical significance. The E7 peptide (EPLQLKM), which exhibits a specific affinity for mesenchymal stem cells (MSCs), is beneficial for modulating cellular functions. In this study, a unique microporous structured carboxymethyl chitosan/sodium alginate membrane with a proper mass ratio is developed by the addition of Poloxam 407 （P407）, which is then functionalized with the E7 affinitive peptide. This membrane, characterized by its microporous structure and E7 peptide functionalization (CSSA/P/E), not only demonstrated favorable mechanical properties, enhanced hydrophilicity, satisfactory biodegradation profile, and excellent biocompatibility, but also synergistically enhanced MSCs recruitment. It is found to promote the proliferation, spreading, and osteogenic differentiation of MSCs in vitro and to accelerate early periosteal regeneration, bone matrix deposition, and vascularization in vivo, leading to effective regeneration of critical-sized bone defects. Overall, this study presents a robust, cell and growth factor-free strategy for bioengineering periosteum, offering a potential solution for the challenging large size bone defects.
研究领域:
组织工程
·
生物材料
·
再生医学
·
干细胞生物学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2021
·
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
·
分子生物学
·
药学
·
生物技术
·
癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
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
·
分子生物学
·
纳米技术
·
基因治疗
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Yuanming Xiao,Yangyang Qu,Xuankai Hu,Jinmin Zhao,Sheng Xu,Li Zheng,Xiaonan Liang
Effective membranes that have the osteogneic potential and the ability to recruit osteoblast precursor cells challenged guided bone regeneration (GBR). Herein, we engineered multifunctional nanofiber membranes by using eletrospun poly(ε-caprolactone) (PCL) and silk fibroin (SF), incorporated with octacalcium phosphate (OCP) and BMSCs-affine peptide (E7) to form the PCL/SF/OCP/E7 (PSOE) nanofiber, wherein the E7 peptide enhances the enrichment of BMSCs, and OCP as osteogenesis promoter. The composite membranes enhance the recruitment and biomineralization processes essential for bone regeneration. Notably, the dual functionality of BMSC recruitment and osteoinduction provides a “recruitment-osteoinduction” strategy that significantly improves bone repair. In vitro analyses confirmed that the PSOE nanofibers have superior hydrophilicity and biocompatibility, and significantly upregulated the expression of osteogenic genes in mesenchymal stem cells, thereby facilitating osteogenic differentiation. In vivo studies using a rat tibial defect model revealed that PSOE nanofibers promoted bone repair within 8 weeks, as validated by micro-CT and histological evaluations. This study highlights the PSOE nanofiber's potential as a promising synthetic periosteum substitute for effective bone regeneration.
研究领域:
生物材料
·
组织工程
·
再生医学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Lujie Zong,Qing Wang,Houyi Sun,Qian Wu,Yaozeng Xu,Huilin Yang,Shujun Lv,Liang Zhang,Dechun Geng
Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degeneration. Unfortunately, currently available clinical drugs are mainly analgesics and cannot alleviate the development of OA. Kartogenin (KGN) has been found to promote the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes for the treatment of cartilage damage in early OA. However, KGN, as a small hydrophobic molecule, is rapidly cleared from the synovial fluid after intra-articular injection. This study synthesized a KGN-loaded nanocarrier based on PLGA/polydopamine core/shell structure to treat OA. The fluorescence signal of KGN@PLGA/PDA-PEG-E7 nanoparticles lasted for 4 weeks, ensuring long-term sustained release of KGN from a single intra-articular injection. In addition, the polyphenolic structure of PDA enables it to effectively scavenge reactive oxygen species, and the BMSC-targeting peptide E7 (EPLQLKM) endows KGN@PLGA/PDA-PEG-E7 NPs with an effective affinity for BMSCs. As a result, the KGN@PLGA/PDA-PEG-E7 nanoparticles could effectively induce cartilage in vitro and protect the cartilage and subchondral bone in a rat ACLT model. This therapeutic strategy could also be extended to the delivery of other drugs, targeting other tissues to treat joint diseases.
研究领域:
生物医学工程
·
药剂学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Engineering
·
2024
·
IF 10.1
Xiao Wang,Shuning Zhang,Ai Zhu,Lingyan Cao,Long Xu,Junjie Wang,Fei Zheng,Xiangkai Zhang,Hongyan Chen,Xinquan Jiang
Given its excellent biological properties and the matching of its elastic modulus with that of human bone tissue, medical polyetheretherketone (PEEK) is considered a desirable candidate for bone-implant materials. However, its poor osseointegrative and antibacterial properties greatly limit its clinical application. To address these concerns, a functional PEEK implant is needed. Herein, a novel photo-responsive multifunctional PEEK-based implant material (sPEEK/BP/E7) with both effective osteogenesis and good disinfection properties was constructed via the self-assembly of black phosphorus (BP) nanosheets, mussel-inspired polydopamine (PDA), and bioactive short peptide E7 on sulfonated PEEK (sPEEK). The versatile micro-/nano-structured PEEK surface provides superior hydrophilicity, a favorable osteogenic microenvironment, and excellent photothermal effects under near-infrared (NIR) irradiation. The in vitro results showed that sPEEK/BP/E7 displays enhanced cytocompatibility and osteogenicity in terms of cell adhesion, proliferation, alkaline phosphatase (ALP) activity, matrix mineralization, and osteogenesis-related gene expression, superior to those of the sPEEK and sPEEK/BP samples. In addition to osteogenesis, the multifunctional coating exhibited strong antibacterial activity against both Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ). Furthermore, it was confirmed in a rat femoral infection model that sPEEK/BP/E7 effectively resisted infection caused by S. aureus under NIR light irradiation and promoted osseointegration in vivo . Thus, this work presents a facile strategy to realize improvement of the “functional integration” of new polymer bone-implant materials and provide new ideas for their clinical application.
研究领域:
生物医学材料
·
组织工程
·
表面改性
✓ 已验证
产品关联
DOI
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
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）