MICROCHIMICA ACTA
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2024
·Vol. 191
·期 2
·1-11
·
IF 5.3
Zhao Zhe,Li Zhixin,Huang Jiahui,Deng Xiaoyu,Jiang Fan,Han Ray P.S.,Tao Yingzhou,Xu Shaohua
Hyaluronidase (HAase) is an important endoglycosidase involved in numerous physiological and pathological processes, such as apoptosis, senescence, and cancer progression. Simple, convenient, and sensitive detection of HAase is important for clinical diagnosis. Herein, an easy-to-operate multicolor visual sensing strategy was developed for HAase determination. The proposed sensor was composed of an enzyme-responsive hydrogel and a nanochromogenic system (gold nanobipyramids (AuNBPs)). The enzyme-responsive hydrogel, formed by polyethyleneimine-hyaluronic acid (PEI-HA), was specifically hydrolyzed with HAase, leading to the release of platinum nanoparticles (PtNPs). Subsequently, PtNPs catalyzed the mixed system of 3,3′,5,5′-tetramethylbenzidine (TMB) and H 2 O 2 to produce TMB 2+ under acidic conditions. Then, TMB 2+ effectively etched the AuNBPs and resulted in morphological changes in the AuNBPs, accompanied by a blueshift in the localized surface plasmon resonance peak and vibrant colors. Therefore, HAase can be semiquantitatively determined by directly observing the color change of AuNBPs with the naked eye. On the basis of this, the method has a linear detection range of HAase concentrations between 0.6 and 40 U/mL, with a detection limit of 0.3 U/mL. In addition, our designed multicolor biosensor successfully detected the concentration of HAase in human serum samples. The results showed no obvious difference between this method and enzyme-linked immunosorbent assay, indicating the good accuracy and usability of the suggested method. Graphical Abstract
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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临床诊断
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2024
·Vol. 48
·期 46
·19462-19471
·
IF 2.7
Wei Guo,Yunhan Huang,Jingrui Chang,Xinyu Wang,Bo Lu
Mesoporous organosilica nanoparticles (MONs) are promising drug carriers with excellent biocompatibility and biodegradability. In the context of the bacterial infection microenvironment, a hyaluronidase (HAase)/glutathione (GSH) dual-responsive degradable nanoplatform based on MON (ICG/CIP@MON@PEI-HA) has been developed for the multimodal treatment of bacterial infection. In this work, ciprofloxacin (CIP) and indocyanine green (ICG) are physically adsorbed into the MON, polyethyleneimine (PEI) is electrostatically adsorbed onto the MON surface, and hyaluronic acid (HA) is grafted onto the amino groups of PEI via the amide bonds. The overexpression of HAase at bacterial infection sites enables HA shell degradation, and positively charged PEI is exposed, which facilitates nanoparticle binding to negatively charged bacteria. Also, owing to the protonation of amine groups, PEI is swelled in the acidic environment of bacterial infection, which favours drug release. Subsequently, overexpressed GSH breaks the disulfide bonds in the MON, triggering structural degradation that inhibits carrier accumulation and accelerates drug release even further. According to in vitro antibacterial evaluations, the antibacterial effect can be enhanced to 100% when phototherapy and pharmaceutical therapy are combined. In vitro cytotoxicity assays have demonstrated that ICG/CIP@MON@PEI-HA possesses excellent biocompatibility. Therefore, this study offers a potential approach for developing biodegradable nanoplatforms for the combined treatment of bacterial infection.
研究领域:
纳米技术
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生物医学工程
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药学
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材料科学
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产品关联
DOI
高影响因子
BMC CANCER
·
2026
·Vol. 26
·期 1
·1086
·
IF 4.1
Dou Bo,Wu Ruiqi,Ma Xiaolai,Hu Changhua,Duan Xiaoqun
Hyaluronidase (HAase) is an enzyme capable of degrading hyaluronic acid (HA). In anti-tumor therapy, HAase can enhance the efficacy of anti-cancer drugs by regulating the tumor microenvironment and overcoming drug delivery barriers, and it can also be used directly to inhibit tumor growth. In this study, we identified a previously uncharacterized HAase (Ph-HAase) from Pedobacter heparinus . After purification, the enzyme was obtained with a 43.08% recovery, a 47.5-fold purification, and a specific activity of 32.32 IU/mg. SDS-PAGE and LC-MS analyses revealed that the molecular weight of Ph-HAase was 79.6 kDa. Ph-HAase exhibited excellent stability at temperatures below 30 °C and within the pH range of 6.5 to 7.5. The enzyme activity was found to be relatively high at pH 6.5 and 45℃. Although HA served as the preferred substrate, Ph-HAase also exhibited degradative activity toward Chondroitin Sulfate (CS) and Dermatan Sulfate (DS). Notably, we found that Ph-HAase induced apoptosis in melanoma B16F10 cells via the mitochondrial pathway, characterized by loss of membrane potential and ROS accumulation, and affected the expression of apoptosis-related genes and proteins. In vivo studies further confirmed its anti-melanoma effect. This study is the first to report HAase derived from P. heparinus and to demonstrate its potential for melanoma treatment.
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DOI
高影响因子
EUROPEAN POLYMER JOURNAL
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2025
·
IF 6.3
Danyang Li,Shizhen Zhao,Yuanpeng Cai,Hui Liu
Single chemotherapy lacked controllability, while smart-responsive hydrogel could deliver drug to specific sites in response to different external stimuli. Hyaluronic acid–Chitosan–Thioketal@Chlorin e6 (HA-CS-TK@Ce6) hydrogel with dual response of ROS and hyaluronidase (HAase) was synthesized by electrostatic interaction force. HA-CS-TK@Ce6 hydrogel loaded with chemotherapeutic drug doxorubicin (DOX) and photosensitizer Ce6 successfully achieved the combined anticancer effect of chemotherapy and photodynamic therapy. Experimental results demonstrated that releasing efficiency of the hydrogel toward DOX could reach 90.6 % in pH = 5 H 2 O 2 solution with HAase at T = 40 ℃. Moreover, HA-CS-TK@Ce6 hydrogel was capable of stimulating Ce6 to produce massive ROS under 650 nm laser irradiation, thus leading to breakage of ROS-cleavable TK and realizing degradation of hydrogel. It was worth mentioning that laser confocal results indicated that MCF-7 cells could successfully uptake Ce6 and DOX, which further proved that HA-CS-TK@Ce6 hydrogel could achieve efficient photodynamic-chemotherapeutic treatment. Therefore, dual-responsive HA-CS-TK@Ce6 hydrogel with excellent biocompatibility and degradability enabled selective and intelligent release of DOX, which would be prospective to improve therapeutic effect of cancer through chemo-photodynamic therapy.
研究领域:
生物材料学
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肿瘤治疗学
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药剂学
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DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
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2022
·
IF 10.319
Dan Li,Danyang Wang,Ye He,Bailong Tao,Xiaoxia Liu,Yulu Yang,Lu Tan,Yuchen Zhang,Jingwei Hu,Weihu Yang,Yu Tang,Kaiyong Cai
Bacterial infection and insufficient osseointegration are critical factors affecting the long-term success of titanium-based implants. Unfortunately, the direct application of antibiotic on Ti implants easily leads to poor cytocompatibility, as well as the production of drug-resistant bacteria. So, in this work, we designed a prospective antibacterial strategy by combining photothermal and ciprofloxacin (CIP). The synergistic effect of photothermal and antibiotic may provide an effective bacteriostatic efficacy without sacrificing osteogenesis at a mild condition of moderate temperature and less antibiotic. Herein, CIP was loaded into mesoporous polydopamine (MPDA) nanoparticles ( [email protected] ), which were anchored on the surface of titanium and finally covered with sodium hyaluronate-catechol (HAc) coating. The hydrophilic HAc layer could inhibit the early adhesion of bacteria, and some bacteria could secrete bacterial hyaluronidase to accelerate the degradation of HAc. This enabled smart enzyme-triggered release of antimicrobials at the site of infection on-demand and avoided unwanted side effects on normal tissues. In addition, NIR light irradiation had a positive influence on both CIP release and MPDA nanoparticle's photothermal effect. Moreover, before anchoring [email protected] , by the construction of hydroxyapatite microstructure on Ti surface with micro-arc oxidation and alkali heat treatment, the ability of bone formation of Ti could be promoted also. Both in vitro as well as in vivo assays demonstrated that functional Ti has an excellent antibacterial effect and osteogenic ability.
研究领域:
生物医学工程
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材料科学
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纳米技术
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生物材料
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组织工程
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Weibiao Wang,Jingui Ma,Hui Yuan,Zhigang Yang,Xinmin He,Mei Wang,Lingling Yang,Fen Ma,Weiman Zhang,Gidion Wilson,Yuping Sa,Guoning Chen,Xueqin Ma
A new bladder cancer diagnosis and HAase inhibitor screening platform was developed. • Biosensor can detect HAase in urine and distinguish patients without preprocessing. • This method shows great potential for rapid screening of HAase inhibitor drugs. • Cinnamon Bark exhibited a significant HAase inhibition effect among 56 herbs. • Cinnamaldehyde was identified as a HAase inhibitor with an IC₅₀ of 396.5 μg/mL. Hyaluronidase (HAase) is a potent urinary biomarker for bladder cancer, yet its clinical detection and the discovery of related inhibitors are often hindered by complex procedures and susceptibility to interference. To address these challenges, this study developed an integrated strategy that combines a dual-phase biosensor with immobilized HAase-based ligand fishing. The HAase-responsive biosensor enables both high-throughput screening of inhibitors from herbal extracts and direct, pretreatment-free analysis of clinical urine samples, effectively distinguishing bladder cancer patients from healthy individuals. Meanwhile, the complementary ligand fishing module allows precise capture and identification of bioactive compounds from complex mixtures, leading to the discovery of cinnamaldehyde as a candidate inhibitor (IC 50 = 396.5 μg/mL). In conclusion, this platform provides a versatile strategy that not only facilitates the rapid discovery of HAase-targeting agents from natural products but also offers a simple and interference-resistant approach for non-invasive monitoring of bladder cancer. Download: Download high-res image (384KB) Download: Download full-size image
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DOI
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2020
·Vol. 412
·期 8
·1915-1923
·
IF 3.637
Ge Minghao,Sun Jiaojiao,Chen Mingli,Tian Jingjing,Yin Huancai,Yin Jian
Due to its important role in tumor development and treatment, hyaluronidase (HAase) has been widely investigated in vitro and in vivo. However, such investigation was limited by the absence of sensitive and in situ detection methods. Herein, a hyaluronic acid (HA) hydrogel based on the fluorescence resonance energy transfer (FRET) effect was constructed for the detection of HAase. FITC and AuNPs were covalently coupled with two HA derivatives respectively to form a fluorescent donor-acceptor pair. In the presence of HAase, the hydrogel established by cross-linking of HA derivatives was hydrolyzed specifically. The FRET effect in the hydrogel disappeared and the fluorescence intensity increased proportionally with the changes in the concentration of the HAase. Experiments proved that the HAase sensing system had a wide response range (0.5–100 U/mL), good anti-interference, and excellent biocompatibility. When the hydrogel was used for 3D culture of lung cancer cells, in situ fluorescent response could be achieved.
Graphical abstract
研究领域:
生物医学工程
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分析化学
·
材料科学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Junjie Liu,Wenyan Yu,Mingxu Han,Wei Liu,Zhenzhong Zhang,Kaixiang Zhang,Jinjin Shi
Magnetic resonance imaging (MRI) contrast agents (CAs) are a powerful tool for disease diagnosis. However, the “always on” state of clinically used CAs affects the specificity of tumor MR imaging in vivo . Herein, we constructed a tumor microenvironment “switch-on” type nanoprobe (TSN) with a distance-dominated property for specific tumor MR imaging, by employed a superparamagnetic hollow mesoporous iron oxide nanoparticle (HMIN) as the carrier to encapsulate T 1 -field CA (Gd), followed by blocking of the mesoporous channel with biocompatible hyaluronic acid (HA). In normal tissues with low-level hyaluronidase (HAase), Gd was restricted inside the HMIN, the distance between the two substances became quite close, and the magnetic field of Gd was interfered by the superparamagnetic HMIN, turning “off” the T 1 -field signal is “turned off”; in contrast, in tumor tissues with high-level HAase, Gd was rapidly released from the HMIN by specifically responding to overexpressed HAase, the distance between the two substances became significantly enlarged, and the magnetic field of Gd was not interfered, thus turning “on” the T 1 -field signal to achieve tumor-specific “switch on” MR imaging in a distance-controlled manner. The tumor/normal T 1 -field signal ratio after TSN treatment increased by 1.9-fold compared with free Gd-DTPA, because of its high Gd loading content, tumor-targeting ability of HA and the tumor-specific property. This distance-controlled switchable nanoprobe provides an alternative strategy for high-resolution tumor imaging with high specificity.
研究领域:
医学成像
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纳米技术
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生物医学工程
·
癌症诊断
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2019
·
IF 13.903
Fenfen Zheng,Chen Wang,Tiantian Meng,Yuqian Zhang,Penghui Zhang,Qi Shen,Yuchao Zhang,Junfeng Zhang,Jianxin Li,Qianhao Min,Jiangning Chen,Jun-Jie Zhu
In vivo monitoring of cargo protein delivery is critical for understanding the pharmacological efficacies and mechanisms during cancer therapy, but it still remains a formidable challenge because of the difficulty in observing nonfluorescent proteins at high resolution and sensitivity. Here we report an outer-frame-degradable nanovehicle featuring near-infrared (NIR) dual luminescence for real-time tracking of protein delivery in vivo. Upconversion nanoparticles (UCNPs) and fluorophore-doped degradable macroporous silica (DS) with spectral overlap were coupled to form a core–shell nanostructure as a therapeutic protein nanocarrier, which was eventually enveloped with a hyaluronic acid (HA) shell to prevent protein leakage and for recognizing tumor sites. The DS layer served as both a container to accommodate the therapeutic proteins and a filter to attenuate upconversion luminescence (UCL) of the inner UCNPs. After the nanovehicles selectively accumulated at tumor sites and entered cancer cells, intracellular hyaluronidase (HAase) digested the outermost HA protective shell and initiated the outer frame degradation-induced protein release and UCL restoration of UCNPs in the intracellular environment. Significantly, the biodistribution of the nanovehicles can be traced at the 710 nm NIR fluorescence channel of DS, whereas the protein release can be monitored at the 660 nm NIR fluorescence channel of UCNPs. Real-time tracking of protein delivery and release was achieved in vitro and in vivo by NIR fluorescence imaging. Moreover, in vitro and in vivo studies manifest that the protein cytochrome c-loaded nanovehicles exhibited excellent cancer therapeutic efficacy. This nanoplatform assembled by the outer-frame-degradable nanovehicles featuring NIR dual luminescence not only advances our understanding of where, when, and how therapeutic proteins take effect in vivo but also provides a universal route for visualizing the translocation of other bioactive macromolecules in cancer treatment and intervention.
研究领域:
生物医学工程
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癌症研究
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纳米技术
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药学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Zekun Li,Yongchun Pan,Shiyu Du,Yayao Li,Chao Chen,Hongxiu Song,Yueyao Wu,Xiaowei Luan,Qin Xu,Xiaoxiang Guan,Yujun Song,Xin Han
Near-infrared (NIR)-light-triggered nanomedicine, including photodynamic therapy (PDT) and photothermal therapy (PTT), is growing an attractive approach for cancer therapy due to its high spatiotemporal controllability and minimal invasion, but the tumor eradication is limited by the intrinsic anti-stress response of tumor cells. Herein, we fabricate a tumor-microenvironment responsive CRISPR nanoplatform based on oxygen-deficient titania (TiO 2- x ) for mild NIR-phototherapy. In tumor microenvironment, the overexpressed hyaluronidase (HAase) and glutathione (GSH) can readily destroy hyaluronic acid (HA) and disulfide bond and releases the Cas9/sgRNA from TiO 2- x to target the stress alleviating regulators, i.e. , nuclear factor E2-related factor 2 (NRF2) and heat shock protein 90 α (HSP90 α ), thereby reducing the stress tolerance of tumor cells. Under subsequent NIR light illumination, the TiO 2- x demonstrates a higher anticancer effect both in vitro and in vivo . This strategy not only provides a promising modality to kills cancer cells in a minimal side-effects manner by interrupting anti-stress pathways but also proposes a general approach to achieve controllable gene editing in tumor region without unwanted genetic mutation in normal environments.
研究领域:
癌症治疗
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纳米技术
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基因编辑
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光疗
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生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Minglong Chen,Bin Chen,Xiaoguang Ge,Qingjie Ma,Shi Gao
One of the main reasons why most cancer patients do not respond well to chemotherapy is that drugs cannot accumulate in tumors at an optimal dose, eventually resulting in failure to prevent cancer cell growth. To improve drug delivery efficiency, we engineered a highly efficient tumor-targeted and stroma-breaking nanocarrier by the modification of iron oxide nanoparticles (IONPs) with a tumor-targeting peptide c(RGDyK) and a hyaluronidase (HAase) on the surface. The yielding nanocomplex, c(RGDyK)-HAase-IONP, targeted the tumor by binding integrin αvβ3 and went deeply into the tumors by the degradation of hyaluronic acid (HA), which was highly expressed in the tumor extracellular matrix (ECM). Good biostability and a low pH preferred drug release profile were characterized for c(RGDyK)-HAase-IONP carrying DOX in vitro. c(RGDyK)-HAase-IONP showed an improved tumor-targeting (2.5 times higher) effect after intravenous injection in the MC38 tumor-bearing mice model, as determined by whole-body fluorescence imaging compared to the non-targeted IONPs without HAase. After 5 systemic treatments, c(RGDyK)-HAase-IONP/DOX (5 mg/kg of equivalent dose of DOX) significantly inhibited MC38 tumor growth (22.1 ± 7.4 times relative to the non-treated group). Elevated apoptosis and reduced proliferation in the tumor cell were detected in the c(RGDyK)-HAase-IONP/DOX treated tumors compared to the control groups. Overall, the highly efficient targeted nanocarrier c(RGDyK)-HAase-IONP demonstrated tremendous potency for improving drug delivery and tumor therapy efficacy by targeted degradation of the dense HA barrier in the tumor ECM. We determined that such a tumor stroma–degrading nanosystem was capable of reducing tumor recurrence and drug resistance and could ultimately improve clinical tumor treatment responses.
研究领域:
癌症治疗
·
纳米技术
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药学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
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