MATERIALS & DESIGN
·
2021
·
IF 7.991
Xiqi Ma,Xiaojuan Wang,Cai Liu,Baosheng Ge,Hua He,Qi Dai,Zhixiong Zhang,Jinyi Yu,Werner M. Nau,Fang Huang
Compared with primary and local tumor, metastasis is more difficult to resect completely and remain the leading cause of death associated with solid tumors. It is therefore pressing to develop effective strategies to prevent and suppress tumor metastasis in its early stages. Heparanase overexpression is significantly associated with increased malignancy and metastasis. Here, we develop a novel heparanase degradable heparin-based microcarrier, HBMA, for specific staining, targeting, and inhibiting tumor cells with high metastatic potential. HBMA is fabricated through self-assembling of three components, positively charged fluorescent gold nanoclusters (KG-AuNCs), heparin polymers (HP), and antisense miRNA-21 oligonucleotides (AM-21), with each component playing multiple roles. Results of confocal microscopy and flow cytometry show that this agent has an excellent capability to label metastatic tumor cells with high selectivity. On the therapeutic side, the results of cell viability assay, wound healing assay, and plate colony formation assay verify that HBMA induces a significant inhibition effect towards the proliferation and migration of the selectively target tumor cells. The heparanase responsive AM-21 delivery, the specific staining, and the efficient tumor cell activity suppression highlight HBMA as a promising cancer theranostic agent to prevent tumor metastasis.
研究领域:
肿瘤学
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分子生物学
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纳米医学
✓ 已验证
DOI
高影响因子
Nanoscale
·
2025
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IF 5.1
Xiaofen Yi,Xiangyu Jin,Huihui Yan,Tong Xu,Lu Chen,Dingyi Yu,Kai Wang,Ping Huang
Anaplastic thyroid cancer (ATC) is aggressive and has a high mortality rate. Doxorubicin (DOX), the first-line chemotherapy drug for ATC, has an insufficient effective concentration and severe cardiac toxicity, limiting its clinical application. Therefore, it is urgent to enhance efficacy of DOX and reduce its toxicity. Designing stimulus-responsive drug delivery systems (DDSs) based on the characteristics of the tumor microenvironment may be a promising approach for the treatment of ATC. We found that heparanase (HPSE) is highly expressed in the tumor microenvironment of ATC but not in normal thyroid tissue. In this study, we successfully constructed and characterized the HPSE-responsive self-assembled carrier TET-HS-NI, which was modified with 3,3,5,5-Tetraiodothyroacetic acid (TET) that targetsαvβ3. DOX was loaded into TET-HS-NI to construct TET-HS-NI/DOX. The zebrafish cell-derived xenograft (CDX) and ATC orthotopic models showed that TET-HS-NI/DOX significantly improved the antitumor efficacy and safety of DOX. In a word , we have constructed a drug delivery system sensitively released DOX in the ATC environment where HPSE overexpressed, increasing the effective concentration at the tumor site and provide a new method for the treatment of ATC.
研究领域:
肿瘤学
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纳米医学
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药物递送
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分子影像
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转化医学
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内分泌肿瘤学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Marine Drugs
·
2021
·Vol. 19
·期 3
·162
·
IF 5.118
Xiang Shi,Ruowei Guan,Lutan Zhou,Zhichuang Zuo,Xuelin Tao,Pin Wang,Yanrong Zhou,Ronghua Yin,Longyan Zhao,Na Gao,Jinhua Zhao
Unique fucosylated glycosaminoglycans (FG) have attracted increasing attention for various bioactivities. However, the precise structures of FGs usually vary in a species-specific manner. In this study, HfFG was isolated fromHolothuria floridanaand purified by anion exchange chromatography with the yield of ~0.9%. HfFG was composed of GlcA, GalNAc and Fuc, its molecular weight was 47.3 kDa, and the -OSO3−/-COO−molar ratio was 3.756. HfFG was depolymerized by a partial deacetylation–deaminative cleavage method to obtain the low-molecular-weight HfFG (dHfFG). Three oligosaccharide fragments (Fr-1, Fr-2, Fr-3) with different molecular weights were isolated from the dHfFG, and their structures were revealed by 1D and 2D NMR spectroscopy. HfFG should be composed of repeating trisaccharide units -{(L-FucS-α1,3-)d-GlcA-β1,3-d-GalNAc4S6S-β1,4-}-, in which sulfated fucose (FucS) includes Fuc2S4S, Fuc3S4Sand Fuc4Sresidues linked to O-3 of GlcA in a ratio of 45:35:20. Furthermore, the heparanase inhibitory activities of native HfFG and oligosaccharide fragments (Fr-1, Fr-2, Fr-3) were evaluated. The native HfFG and its oligosaccharides exhibited heparanase inhibitory activities, and the activities increased with the increase of molecular weight. Additionally, structural characteristics such as sulfation patterns, the terminal structure of oligosaccharides and the presence of fucosyl branches may be important factors affecting heparanase inhibiting activity.Keywords:Holothuria floridana;fucosylated glycosaminoglycans;oligosaccharide;chemical structure;heparanase
研究领域:
海洋生物学
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生物化学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2022
·
IF 6.556
Yayun Gu,Lizhong Peng,Weihua Ding,Yang Wang,Xuhui Zeng
Heparanase (HPA) is a multifaceted endo -β-glucuronidase, and its dysregulation facilitates cancer metastasis. Developing techniques for fast and sensitively monitoring HPA enzymatic activity is crucial for searching for molecular therapies targeting HPA. Herein, we developed a novel fluorescence resonance energy transfer (FRET)-based nanoprobe AuNCs-LMWH-AuNRs, with AuNCs@GSH-cys and AuNRs/end-NH 2 /side-SiO 2 attached to the non-reducing terminus and reducing terminus of low molecular weight heparin (LMWH), respectively. AuNCs@GSH-cys exhibited an absolute quantum yield of 1.1%. The absorption spectra of AuNRs/end-NH 2 /side-SiO 2 (825 nm for maximum longitudinal absorption) and the emission spectra of AuNCs@GSH-cys (824 nm for maximum emission) were precisely overlapping, further enhancing the efficiency of FRET. In the presence of HPA, the LMWH nanoprobe exhibited an ultrasensitive response with excitation/emission wavelength (lambda (ex) = 560 nm, lambda (em) = 824 nm). The probe presented a wide linear dynamic detection range (LDR) of 0.125 ng/μL - 0.01 μg/μL in vitro with a limit of detection (LODs) of 82.15 pM (0.43 pg/μL). The excellent selectivity and good fluorescence turn-on efficiency of the probe made it possible for one-step detection of cellular heparanase activity. High throughput screening of HPA inhibitors also can be accomplished using the highly efficient LMWH nanoprobe.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2020
·
IF 10.317
Jun Zhang,Jie Yang,Tiantian Zuo,Siyu Ma,Nadira Xokrat,Zongwei Hu,Zhihua Wang,Rui Xu,Yawen Wei,Qi Shen
The normal chemotherapy only induces the intracellular apoptosis pathway to promote primary tumor cells death, while not inhibit tumor metastasis. Herein, we proposed a kind of heparanase (HPSE)-driven sequential released nanoparticles , which modified with β-cyclodextrin (β-CD) grafted heparin (NLC/H(D + F + S) NPs) co-loading with doxorubicin (DOX), ferrocene (Fc), and TGF-β receptor inhibitor (SB431542). NLC/H(D + F + S) NPs successfully inhibited breast cancer metastasis by intracellular and extracellular hybrid mechanism. DOX and Fc loaded in NLC/H(D + F + S) NPs effectively enhanced intracellular ROS level to activate ferroptosis pathway, the enhanced ROS also induced the apoptosis pathway and decreased MMP-9 expression to synergize with ferroptosis for tumor therapy. In extracellular site, SB431542 was sequentially released by HPSE-driven, which blocked tumor metastasis by modulating tumor microenvironment , decreasing TAFs activation, and reducing the secretion of TGF-β. In addition, anti-tumor immune response induced by ferroptosis further strengthened the effect of tumor therapy. Finally, under the help of intracellular and extracellular mechanisms launched by NLC/H(D + F + S) NPs, the satisfactory anti-tumor metastasis effect was obtained in the in vivo anti-tumor assays. Therefore, NLC/H(D + F + S) NPs was a novel dosage regimen for breast cancer therapy through intracellular and extracellular mechanisms, in which ferroptosis induced by ROS played an important role.
研究领域:
癌症治疗
·
纳米技术
·
药理学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2026
·
IF 13.2
Pin Wang,Na Gao,Qijiang Mao,Lutan Zhou,Yu Wang,Ying Pan,Fengyun Wu,Penghao Kang,Zanyang Min,Yujun Ma,Huifang Sun,Xiang Shi,Mingzhu Yang,Fuchuan Li,Yiyin Zhang,Jinhua Zhao
White jade snail (a bred albino variant of Achatina fulica ) is widely used in China as an edible and medicinal resource. Previous studies have reported the overall structural characteristics of its glycosaminoglycan (GAG) at the polymer level; however, precise oligosaccharide evidence and structure-function relevance have remained insufficient. In this study, the heparan-like GAG from farmed white jade snails (AfH) was structurally elucidated using a bottom-up strategy based on well-defined oligosaccharides generated by β-eliminative and deaminative depolymerization, revealing a highly regular repeating unit -[4-D-GlcNAc-α1,4-L-IdoA 2S -α1,]-. Notably, alkaline processing was demonstrated to induce artificial structural alterations, including 2-O-desulfation of IdoA 2S , conversion of IdoA to GalA, and epimerization of GlcNAc to ManNAc. AfH exhibited potent heparanase inhibitory activity while showing negligible anticoagulant and P-selectin inhibition, with activity positively correlated with molecular weight and sulfate content. Structural variations showed distinct biological impacts, ManNAc introduction in a tetrasaccharide (Tetra-2) enhanced heparanase inhibition. Functionally, AfH significantly suppressed 4T1 cell migration and invasion and reduced pulmonary metastasis in mice. This work establishes AfH as a natural resource abundant, well-defined, non-anticoagulant heparan-like GAG with strong anti-metastatic potential, while highlighting alkaline processing as a critical determinant of GAG structural integrity and bioactivity.
✓ 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）