TALANTA
·
2024
·
IF 5.6
Qiang Tang,Xiaoling Huang,Guangxing Liu,Hongran Huang,Jiayi Zhang,Jihua Wei,Yuanxun Gong,Qianli Tang,Kai Zhang,Xianjiu Liao
This study introduces a novel electrochemical biosensor for detecting Matrix Metalloproteinase-2 (MMP-2), a key biomarker in cancer diagnostics and tissue remodeling. The biosensor is based on a dual-amplification strategy utilizing T7 RNA polymerase isothermal amplification and CRISPR-Cas12a technology. The principle involves the release of a DNA template in the presence of MMP-2, leading to RNA synthesis by T7 RNA polymerase. This RNA activates CRISPR-Cas12a, which cleaves a DNA probe on the electrode surface, resulting in a measurable electrochemical signal.The biosensor demonstrated exceptional sensitivity, with a detection limit of 2.62 fM for MMP-2. This high sensitivity was achieved through the combination of transcriptional amplification and the collateral cleavage activity of CRISPR-Cas12a, which amplifies the signal. The sensor was able to detect MMP-2 across a wide dynamic range from 2 fM to 1 nM, showing a strong linear correlation between MMP-2 concentration and the electrochemical signal. In practical applications, the biosensor accurately detected elevated levels of MMP-2 in cell culture supernatants from HepG2 liver cancer cells, distinguishing them from normal LO2 liver cells. The use of an MMP-2 inhibitor confirmed the specificity of the detection. These results underscore the biosensor's potential for clinical diagnostics, particularly in early cancer detection and monitoring of tissue remodeling activities. The biosensor's design allows for rapid, point-of-care testing without the need for complex laboratory equipment, making it a promising tool for personalized healthcare and diagnostic applications.
研究领域:
生物传感器
·
癌症生物学
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分子诊断
·
电化学
·
生物技术
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xinmin Zheng,Xiang Li,Guolin Shi,Yidan Zhou,Jinxiao Yan,Hao Zhang,Xiru Liu,Jiangong Zhang,Yu Liu,Liangliang Dai,Hui Yang
The low targeting of immunity regulators & chemotherapy drugs and immune tolerance in the tumor microenvironment significantly hindered the chemo-immunotherapy effect. In this work, an MMP-2/GSH-responsive nanobomb loading Resiquimod (R848) and prodrug Cisplatin (Pt) with hierarchical drug delivery and tumor associated macrophages (TAMs) polarization traits was designed for improved chemo-immunotherapy. The Pt-carrying dendrimers penetrate the depth of tumor tissues under MMP-2 and activate the cytotoxicity of Pt prodrug in response to GSH, causing effective tumor damage and enhancing immunogenicity. Meanwhile, R848 is effectively uptake by TAMs, which were re-educated and then greatly relieved immune resistance. In vitro and in vivo results collectively revealed that the nanosystem could not only overcome the barrier of tumor penetration and the heterogeneity action sites of drugs but also re-educate TAMs and suppress immune evasion via activating extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signal pathway regulated by heparin binding EGF like growth factor ( Hbegf ) gene. The gene silencing or knockout in vitro and in vivo demonstrated that Hbegf could regulate the re-education of TAMs and the progression of tumors.
研究领域:
肿瘤学
·
免疫学
·
药剂学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2022
·
IF 10.383
Huifang Liu,Dongqin Lei,Jiong Li,Jing Xin,Luwei Zhang,Lei Fu,Jing Wang,Weihui Zeng,Cuiping Yao,Zhenxi Zhang,Sijia Wang
Combining photodynamic therapy (PDT) with natural killer (NK) cell-based immunotherapy has shown great potential against cancers, but the shedding of NK group 2, member D ligands (NKG2DLs) on tumor cells inhibited NK cell activation in the tumor microenvironment. Herein, we assembled microenvironment-/light-responsive bio-nanosystems (MLRNs) consisting of SB-3CT-containing β-cyclodextrins (β-CDs) and photosensitizer-loaded liposomes, in which SB-3CT was considered to remodel the tumor microenvironment. β-CDs and liposomes were linked by metalloproteinase 2 (MMP-2) responsive peptides, enabling sequential release of SB-3CT and chlorin e6 triggered by the MMP-2-abundant tumor microenvironment and 660 nm laser irradiation, respectively. Released SB-3CT blocked tumor immune escape by antagonizing MMP-2 and promoting the NKG2D/NKG2DL pathway, while liposomes were taken up by tumor cells for PDT. MLRN-mediated photo-immunotherapy significantly induced melanoma cell cytotoxicity (83.31%), inhibited tumor growth (relative tumor proliferation rate: 1.13% of that of normal saline) in the xenografted tumor model, and enhanced tumor-infiltrating NK cell (148 times) and NKG2DL expression (9.55 and 16.52 times for MICA and ULBP-1, respectively), achieving a synergistic effect. This study not only provided a simple insight into the development of new nanomedicine for programed release of antitumor drugs and better integration of PDT and immunotherapy but also a novel modality for clinical NK cell-mediated immunotherapy against melanoma.
研究领域:
癌症治疗
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纳米技术
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免疫学
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药理学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2017
·
IF 7.504
Min Han,Ming-Yi Huang-Fu,Wang-Wei Guo,Ning-Ning Guo,JieJian Chen,Hui-Na Liu,Zhi-Qi Xie,Meng-Ting Lin,Qi-Chun Wei,Jian-Qing Gao
Currently, the limited penetration of nanoparticles remains a major challenge for antitumor nanomedicine to penetrate into the tumor tissues. Herein, we propose a size-shrinkable drug delivery system based on a polysaccharide-modified dendrimer with tumor microenvironment responsiveness for the first time to our knowledge, which was formed by conjugating the terminal glucose of hyaluronic acid (HA) to the superficial amidogen of poly(amidoamine) (PAMAM), using a matrix metalloproteinase-2 (MMP-2)-cleavable peptide (PLGLAG) via click reaction. These nanoparticles had an initial size of ∼200 nm, but once deposited in the presence of MMP-2, they experienced a dramatic and fast size change and dissociated into their dendrimer building blocks (∼10 nm in diameter) because of cleavage of PLGLAG. This rapid size-shrinking characteristic not only promoted nanoparticle extravasation and accumulation in tumors benefited from the enhanced permeability and retention effect but also achieved faster nanoparticle diffusion and penetration. We have further conducted comparative studies of MMP-2-sensitive macromolecules (HA-pep-PAMAM) and MMP-2-insensitive macromolecules (HA–PAMAM) synthesized with a similar particle size, surface charge, and chemical composition and evaluated in both monolayer cells and multicellular spheroids. The results confirmed that the enzyme-responsive size shrink is an implementable strategy to enhance drug penetration and to improve therapeutic efficacy. Meanwhile, macromolecule-based nanoparticles with size-variable characteristics not only promote drug penetration, but they can also be used as gene delivery systems, suggesting great potential as nano-delivery systems.
研究领域:
纳米医学
·
癌症治疗
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药物递送系统
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生物材料
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肿瘤微环境工程
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Wei-Hai Chen,Xiao-Ding Xu,Hui-Zhen Jia,Qi Lei,Guo-Feng Luo,Si-Xue Cheng,Ren-Xi Zhuo,Xian-Zheng Zhang
A novel strategy to construct a therapeutic system based on functionalized AuNPs which can specifically respond to tumor microenvironment was reported. In the therapeutic system, doxorubicin was conjugated to AuNPs via thiol–Au bond by using a peptide substrate, CPLGLAGG, which can be specifically cleaved by the protease. In vivo study shows that after injection of the functionalized AuNPs to the tumor-bearing mice, the over-expressed protease of MMP-2 in tumor tissue and intracellular GSH can lead to the rapid release of the anti-tumor drug (doxorubicin) from the functionalized AuNPs to inhibit tumor growth and realize fluorescently imaging simultaneously. The functionalized AuNPs with tumor-triggered drug release property can further improve the efficacy and reduce side effects significantly.
研究领域:
纳米医学
·
肿瘤学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Qisheng Luo,Chuanhua Zheng,Yongning Huang,Linghuan Liang,Yuanxun Gong,Jiayi Zhang,Qianli Tang,Kai Zhang,Xianjiu Liao
Lead-halide perovskites offer bright electrochemiluminescence (ECL) but suffer from aqueous instability and Pb 2+ safety concerns. We construct a CsPbBr 3 @PDA–Au nanointerface that couples polydopamine (PDA) passivation with Au-assisted charge transfer, integrated into a peptide-to-CRISPR/Cas12a amplification scheme for ultrasensitive detection of matrix metalloproteinase-2 (MMP-2). PDA conformally coats CsPbBr 3 , suppressing trap-mediated quenching and mitigating Pb 2+ release, while providing catechol/amine anchors for a tetrahedral DNA scaffold bearing a ferrocene-labeled hairpin. Upon MMP-2 cleavage of a GPLG↓VRG peptide–DNA chimera, the released strand activates Cas12a trans-cleavage, removing the proximal quencher and switching the interface from “off” to “on.” Under unified processing (baseline subtraction and renormalization), the platform achieves a 5.6 aM detection limit with high selectivity over non-target proteases and excellent inter-device reproducibility (triplicate error bars reported). TEM/HRTEM visualize uniform nanocubes; XPS/FTIR evidence PDA catechol/quinone/amine coordination; XRD confirms phase-pure CsPbBr 3 ; and corrected CV/EIS analyses verify accelerated interfacial kinetics after Au decoration. The sensor retains ∼98 % intra-day and ≥91 % 7-day signal, supporting operational robustness. By integrating interfacial stabilization, catalytic electron transfer, and molecular amplification, this modular design advances eco-conscious, perovskite-based ECL diagnostics for low-abundance protease monitoring and broader clinical bioanalysis.
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Yongju He,Xiangjie Tian,Xingyu Fan,Xiyu Gong,Songwen Tan,Anqiang Pan,Shuquan Liang,Hui Xu,Fangfang Zhou
The poor penetration of nanocarriers within tumor dense extracellular matrices (ECM) greatly restricts the access of anticancer drugs to the deep tumor cells, resulting in low therapeutic efficacy. Moreover, the high toxicity of the traditional chemotherapeutics inevitably causes undesirable side effects. Herein, taking the advantages of biosafe H2 and small-sized nanoparticles in diffusion within tumor ECM, we develop a matrix metalloprotease 2 (MMP-2) responsive size-switchable nanoparticle (UAMSN@Gel-PEG) that is composed of ultrasmall amino-modified mesoporous silica nanoparticles (UAMSN) wrapped within a PEG-conjugated gelatin to deliver H2 to the deep part of tumors for effective gas therapy. Ammonia borane (AB) is chosen as the H2 prodrug that can be effectively loaded into UAMSN by hydrogen-bonding adsorption. Gelatin is used as the substrate of MMP-2 to trigger size change and block AB inside UAMSN during blood circulation. PEG is introduced to further increase the particle size and endow the nanoparticle with long blood circulation to achieve effective tumor accumulation via the EPR effect. After accumulation into the tumor site, MMP-2 promptly digests gelatin to expose UAMSN loading AB for deep tumor penetration. Upon stimulation by the acidic tumor microenvironment, AB decomposes into H2 for further intratumor diffusion to achieve effective hydrogen therapy. Consequently, such a simultaneous deep tumor penetration of nanocarriers and H2 results in an evident suppression on tumor growth in a 4T1 tumor-bearing model without any obvious toxicity on normal tissues. Our synthetic nanosystem provides a promising strategy for the development of nanomedicines with enhanced tumor permeability and good biosafety for efficient tumor treatment.
研究领域:
肿瘤学
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纳米医学
·
生物材料
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Feng Wu,Yu Huang,Xian Yang,Jing-Jing Hu,Xiaoding Lou,Fan Xia,Yanlin Song,Lei Jiang
Determining the expression level of biomarkers is crucial for disease diagnosis. However, the low abundance of biomarkers in the early stage makes the detection extremely difficult by traditional aggregation-induced emission (AIE)-based fluorescent probes. Here, by tuning the intermolecular interaction, a two steps-based MP/NPs-SLIPS sensing system is designed for ultrasensitive detection of the tumor marker matrix metalloproteinase-2 (MMP-2). During the sensing process, aggregation of AIE residual could be intensified through the electrostatic absorption by negatively charged nanoparticles (NPs), as well as the confined space formed by the self-assembly of NPs to photonic crystals (PCs) on slippery lubricant-infused porous substrates (SLIPS). The fluorescent signals obviously increased with a strengthened aggregation degree, which contributes to improved sensitivity. Thus, the limit of detection is decreased to 3.7 ng/mL for MP/NPs-SLIPS sensing system, which could be used for detecting the MMP-2 secreted by tumor cells directly. This strategy also demonstrated its potential applications as high-throughput detection devices and will be of significance for the ultrasensitive analysis of biomarkers.
研究领域:
生物化学
·
医学诊断
·
材料科学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Yaozhi Zhang,Menglu Jiang,Shiqi Zhang,Aimeng Dong,Fenghua Zhang,Yanju Liu,Huiping Yuan,Jinsong Leng
Traditional hydrogel-based drug delivery systems face critical limitations, including poor toughness and adhesion, and low drug utilization efficiency, which collectively limit their efficacy in glaucoma treatment. Deep eutectic solvents (DESs) can effectively address these limitations because they are structurally tunable and exhibit high rates of drug dissolution. Herein, we apply β-cyclodextrin and phytic acid to prepare a novel DES, which was used to fabricate a deep eutectic smart gel drug delivery system (DSGS). The DES establish multi-hydrogen-bonded shielding networks with polymer chains, endowing the DSGS with an ocular tissue-matched modulus and a high toughness of 5.94 MJ·m − 3 . Notably, the DSGS enables precise drug release in response to dual stimuli: matrix metalloproteinase-2 and temperature. We employ 4D printing technology to engineer a novel glaucoma drainage device (GDD) from the DSGS loaded with an antifibrotic drug for glaucoma treatment. Based on the synergistic effect of DSGS and the drug, the GDD regulates intraocular pressure (IOP), suppresses fibrosis, and restructures the extracellular matrix collagen architecture in vivo. Furthermore, the DSGS is injectable and exhibits strong tissue adhesion. Following minimally invasive implantation into the conjunctiva, a stable IOP was maintained for 30 days. This innovative design represents a promising direction for future drug delivery.
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DOI
高影响因子
METHODS
·
2025
·
IF 4.3
Wensi Li,Zhichao Tang,Xiang Zhu,Beijuan Wang,Xiuqin Zhang,Ze Ji,Suhang Cheng
In this work, an electrochemiluminescence (ECL) biosensor integrating T7 RNA polymerase amplification and CRISPR/Cas13a-mediated signal enhancement was developed for the ultrasensitive detection of matrix metalloproteinase-2 (MMP-2), a key biomarker associated with chronic inflammatory diseases such as COPD. A peptide nucleic acid (PNA) probe was designed to respond specifically to MMP-2 cleavage, enabling the release of DNA templates for subsequent T7 RNA polymerase-driven transcription amplification. The generated RNA triggers the collateral cleavage activity of CRISPR/Cas13a, resulting in a significant amplification of the ECL signal. The biosensor’s surface was constructed using a AuNPs/Ti 3 C 2 Tx/Ru(II)-PEI nanocomposite, which enhanced signal transduction and stability. Under optimized conditions, the proposed biosensor achieved a detection limit as low as 62.05 fM, demonstrating superior sensitivity compared to conventional methods, as summarized in Table 1 . The platform also exhibited excellent specificity and anti-interference capability, ensuring reliable detection of MMP-2 in complex biological samples. This study provides a simple yet highly efficient strategy for enzymatic biomarker detection, offering great potential for clinical applications in early disease diagnosis and monitoring.
研究领域:
生物传感器
·
分子诊断
·
CRISPR技术
·
纳米技术
·
慢性阻塞性肺疾病
·
酶检测
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
·
2024
·
IF 6.1
Jihong Ma,Haiyan Yang,Xue Tian,Fanhu Meng,Xiaoqing Zhai,Aimei Li,Chuntao Li,Min Wang,Guohui Wang,Chunbo Lu,Jingkun Bai
Conventional chemotherapeutic agents are limited by their lack of targeting and penetration and their short retention time, and chemotherapy might induce an immune suppressive environment. Peptide self-assembly can result in a specific morphology, and the resulting morphological changes are stimuli responsive to the external environment, which is important for drug permeation and retention of encapsulated chemotherapeutic agents. In this study, a polypeptide (Pep1) containing the peptide sequences PLGLAG and RGD that is responsive to matrix metalloproteinase 2 (MMP-2) was successfully developed. Pep1 underwent a morphological transformation from a spherical structure to aggregates with a high aspect ratio in response to MMP-2 induction. This drug delivery system (DI/Pep1) can transport doxorubicin (DOX) and indomethacin (IND) simultaneously to target tumor cells for subsequent drug release while extending drug retention within tumor cells, which increases immunogenic cell death and facilitates the immunotherapeutic effect of CD4 + T cells. Ultimately, DI/Pep1 attenuated tumor-associated inflammation, enhanced the body's immune response, and inhibited breast cancer growth by combining the actions of DOX and IND. Our research offers an approach to hopefully enhance the effectiveness of cancer treatment.
研究领域:
肿瘤学
·
药剂学
·
分子生物学
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DOI
PubMed
高影响因子
RSC Advances
·
2025
·Vol. 15
·期 3
·1507-1513
·
IF 4.6
Wei Li,Yan Wang,Hongkun Miao,Maohui Yan,Chen Liu,Yu Wang,Jianjun Zhang,Zhiguang Fu
Oral squamous cell carcinoma is one of the most common types of cancer. Surgical resection is one of the most important treatments at present. However, patients often suffer from regional recurrence after surgery. Therefore, new strategies for combination therapy need to be investigated. This work identified a smart injectable hydrogel system co-delivering DOX and sunitinib nanoparticles. The nano drugs are continuously released from the hydrogels and effectively taken up by cells. The nano drugs in the hydrogel can inhibit tumor cell viability and induce cancer cell apoptosis in vitro. The drug-loaded hydrogel could control the recurrence of subcutaneous xenograft tumors, prolong the survival time, and have no obvious toxicity in nude mice. These findings suggest that this smart injectable hydrogel system may provide new ideas for the comprehensive treatment of oral squamous cell carcinoma.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 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）