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NMOFs
SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

DNA bridged polycrystalline Cu2+-NMOFs for electrochemical detection of mesenchymal circulating tumor cells

Ying Peng,Xiong Zhao,Menglu Li,Yin Yue,Chengying Pan,Taiyuan Li,Sha Ou,Zuquan Hu

The analysis of mesenchymal circulating tumor cells (CTCs) with enhanced migratory is important in the diagnosis and metastasis prediction of cancer. In this work, an efficient electrochemical biosensor has been proposed for the sensitive analysis of mesenchymal CTCs. In our design, the capture antibody modified on the electrode surface can specifically recognize cell-surface vimentin, which is a specific biomarker of mesenchymal CTCs. In the meantime, polycrystalline Cu 2+ -NMOFs with excellent mimic peroxidase property assembled by functional nucleic acids are used as the signal probes . After capturing the mesenchymal CTCs with the capture antibody, the cholesterol-labeled functional nucleic acids modified on the Cu 2+ -NMOFs polycrystalline structures can serve as an anchor to insert into the cell membrane while bringing the polycrystalline Cu 2+ -NMOFs to the surface of the electrode. Consequently, an obvious enhanced signal is generated for sensitive quantitative of mesenchymal CTCs ranging from 2 × 10 1 to 10 4 cell mL −1 with a detection limit of 5 cell mL −1 . Moreover, the biosensor can be applied to quantitative analysis of mesenchymal CTCs in blood samples of clinical bladder cancer patients with high selectivity and anti-interference ability, showing the great prospect for clinical cancer diagnosis.

研究领域: 生物医学工程 · 癌症诊断 · 分析化学
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International Journal of Nanomedicine · 2022 · IF 7.033

Fluorescent Imaging-Guided Chemo- and Photodynamic Therapy of Hepatocellular Carcinoma with HCPT@NMOFs-RGD Nanocomposites

Yue Shang,Hui Zhang,Yajia Cheng,Peipei Cao,Jianlin Cui,Xuebo Yin,Saijun Fan,Yuhao Li

Background Hepatocellular carcinoma (HCC), arising from hepatocytes, is the most common primary liver cancer. It is urgent to develop novel therapeutic approaches to improve the grim prognosis of advanced HCC. 10-hydroxycamptothecin (HCPT) has good antitumor activity in cells; however, its hydrophobicity limits its application in the chemotherapy of HCC. Recently, nanoscale porphyrin metal-organic frameworks have been used as drug carriers due to their low biotoxicity and photodynamic properties.Methods Nanoscale zirconium porphyrin metal-organic frameworks (NMOFs) were coated with arginine-glycine-aspartic acid (RGD) peptide to prepare NMOFs-RGD first. The HepG2 cell line, zebrafish embryos and larvae were used to test the biotoxicity and fluorescence imaging capability of NMOFs-RGD both in vitro and in vivo. Then, NMOFs were used as the skeleton, HCPT was assembled into the pores of NMOFs, while RGD peptide was wrapped around to synthesize a novel kind of nanocomposites, HCPT@NMOFs-RGD. The tissue distribution and chemo- and photodynamic therapeutic effects of HCPT@NMOFs-RGD were evaluated in a doxycycline-induced zebrafish HCC model and xenograft mouse model.Results NMOFs-RGD had low biotoxicity, good biocompatibility and excellent imaging capability. In HCC-bearing zebrafish, HCPT@NMOFs-RGD were specifically enriched in the tumor by binding specifically to integrin αvβ3 and led to a reduction in tumor volume. Moreover, the xenografts in mice were eliminated remarkably following HCPT@NMOFs-RGD treatment with laser irradiation, while little morphological change was found in other main organs.Conclusion The nanocomposites HCPT@NMOFs-RGD accomplish tumor targeting and play synergistic chemo- and photodynamic therapeutic effects on HCC, offering a novel imaging-guided drug delivery and theranostic platform.

研究领域: 肿瘤学 · 药学 · 生物医学工程 · 分子生物学
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JOURNAL OF NANOBIOTECHNOLOGY · 2025 ·Vol. 23 ·期 1 ·1-14 · IF 12.6

Remodeling tumor microenvironment using prodrug nMOFs for synergistic cancer therapy

Dong Junliang,Ding Jindong,Luo Shifan,Li Ruoshui,Wang Yi,Xiao Bing,Pei Yuxin,Chen Xiaoyuan,Sun Wenjing,Pei Zhichao

Metal–organic frameworks (MOFs) hold tremendous potential in cancer therapy due to their remarkable structural and functional adaptability, enabling them to serve as nanocarriers for biopharmaceuticals and nanoreactors for organizing cascade bioreactions. Nevertheless, MOFs are predominantly utilized as biologically inactive carriers in most cases. Developing nanoscale prodrug MOFs suitable for biomedical applications remains a huge challenge. In this study, we have designed a novel prodrug nano-MOFs (nMOFs, named DCCMH) using metformin (Met) and α-cyano-4-hydroxycinnamic acid (CHCA) as ligands for coordination self-assembly with CuCl2, followed by loading of doxorubicin (DOX) and surface modification with hyaluronic acid (HA). Upon internalization by cancer cells, DCCMH releases Cu2+/+, CHCA, Met, and DOX in response to high levels of glutathione (GSH) and hydrogen peroxide (H2O2) within the tumor microenvironment (TME); Cu+ catalyzes the conversion of H2O2 to ·OH via the Fenton reaction while it was oxidized to Cu2+, which was subsequently further de-consumed of GSH; CHCA induces a further decrease in intracellular pH and promotes Fenton reactions by inhibiting lactate efflux; Met up-regulates tyrosine kinase activity and enhances the chemotherapy of DOX. With the ability to synergistically combine chemo/chemodynamic therapy (CT/CDT) and remodel the TME, the DCCMH NPs inhibit murine hepatoma effectively. This study presents a feasible strategy for fabricating prodrug nMOFs which are capable of remodeling TME to improve efficacy through synergistic cancer therapy.Graphical abstract

研究领域: 生物医学工程 · 肿瘤学 · 纳米医学
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CHEMISTRY OF MATERIALS · 2017 · IF 9.466

Zr-Based MOFs Shielded with Phospholipid Bilayers: Improved Biostability and Cell Uptake for Biological Applications

Jian Yang,Xiaojing Chen,Yongsheng Li,Qixin Zhuang,Peifeng Liu,Jinlou Gu

For practical biomedical applications, the stabilization of nanoscale metal–organic frameworks (NMOFs) in the presence of phosphate is of prime importance but remains a significant challenge because of the inevitable and strong driving force between metal clusters and phosphate species to form metal-phosphate in physiological environments. Through shielding Zr-NMOFs within the continuous phospholipid bilayers (PBLs), herein, we figured out a unique way to protect the vulnerable coordination bonds in their frameworks from the attack of phosphate. To exemplify the facility of constructing PBLs on Zr-NMOFs core, a porphyrinic NMOF of PCN-223 (standing for a platform with broad biological applications) was elaborated using a triethylamine (TEA)-modulated strategy. TEA could not only control the phase transformation of porphyrinic MOFs to achieve pure-phase PCN-223 crystals but also minimize their particles size down to sub-200 nm. Negative-stained TEM, FT-IR and XPS techniques revealed that PBLs could be closely coated onto the surface of nanoPCN-223, thanks to the strong Zr–O–P chemical complexation between Zr-NMOFs and phospholipid. The resultant coated nanoPCN-223 exhibited significantly enhanced phosphatic-resistance in phosphate buffer solution (PBS) and presented exceptional stability in harsh chemical environments. Furthermore, the MOFs-supported PBLs could effectively provide a stable biocompatible interface for subsequent cell culture and improve their biocompatibility, cellular uptake efficiency and real biostability of NMOFs in cellular environments. This study offers an alternative system for forming stable PBLs supported on NMOFs, and represents the first example of stabilizing Zr-NMOFs free from the attack of phosphate species in biological media.

研究领域: 纳米技术 · 生物医学工程 · 材料科学 · 生物材料
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JOURNAL OF NANOBIOTECHNOLOGY · 2022 ·Vol. 20 ·期 1 ·1-22 · IF 9.429

Synergistic photothermal-photodynamic-chemotherapy toward breast cancer based on a liposome-coated core–shell AuNS@NMOFs nanocomposite encapsulated with gambogic acid

Li Rong-Tian,Zhu Yi-Dan,Li Wen-Ya,Hou Ying-Ke,Zou Yi-Ming,Zhao Ying-Hua,Zou Quan,Zhang Wen-Hua,Chen Jin-Xiang

A multifunctional nanoplatform with core–shell structure was constructed in one-pot for the synergistic photothermal, photodynamic, and chemotherapy against breast cancer. In the presence of gambogic acid (GA) as the heat-shock protein 90 (HSP90) inhibitor and the gold nanostars (AuNS) as the photothermal reagent, the assembly of Zr4+ with tetrakis (4-carboxyphenyl) porphyrin (TCPP) gave rise to the nanocomposite AuNS@ZrTCPP-GA (AZG), which in turn, further coated with PEGylated liposome (LP) to enhance the stability and biocompatibility, and consequently the antitumor effect of the particle. Upon cellular uptake, the nanoscale metal − organic framework (NMOF) of ZrTCPP in the resulted AuNS@ZrTCPP-GA@LP (AZGL) could be slowly degraded in the weak acidic tumor microenvironment to release AuNS, Zr4+, TCPP, and GA to exert the synergistic treatment of tumors via the combination of AuNS-mediated mild photothermal therapy (PTT) and TCPP-mediated photodynamic therapy (PDT). The introduction of GA serves to reduce the thermal resistance of the cell to re-sensitize PTT and the constructed nanoplatform demonstrated remarkable anti-tumor activity in vitro and in vivo. Our work highlights a facile strategy to prepare a pH-dissociable nanoplatform for the effective synergistic treatment of breast cancer.Graphical Abstract

研究领域: 癌症研究 · 纳米技术 · 药学 · 生物医学工程
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