Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 41
·6716-6725
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IF 4.872
Yi Cao,Min Liu,Kunchi Zhang,Jingjin Dong,Guangyue Zu,Yang Chen,Tingting Zhang,Dangsheng Xiong,Renjun Pei
Macromolecular contrast agents (CAs) labeled with targeting molecules are gaining remarkable interest as promising materials overcoming the defects of small-molecule CAs. Designed on the basis of biocompatible poly(glycerol) (PG), a linear macromolecular contrast agent (CA) was synthesized with a composition of PG as a backbone and partial hydroxyl connected with gadolinium labeled poly(L-lysine) dendrons, where folic acid was also conjugated. This linear CA exhibited higher relaxivity (7.04 mM−1 S−1) relative to Magnevist® (3.98 mM−1 S−1), and showed negligible toxicity determined by WST assay and histological analysis. In vitro and in vivo magnetic resonance imaging (MRI) measurements presented obvious target specificity to KB cells and tumor. Moreover, high signal enhancement was observed in the tumor region at various time points after intravenous injection to ensure the long time window for imaging. All the findings make it an attractive candidate for tumor-targeted MRI CAs.
研究领域:
生物医学工程
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医学影像学
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材料科学
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DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
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2022
·Vol. 46
·期 20
·9658-9665
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IF 3.925
Bo Song,Mengyan Li,Junyu Ren,Qi Liu,Xinyi Wen,Wenzhu Zhang,Jingli Yuan
The combination of complementary optical imaging and magnetic resonance imaging (MRI) techniques evolved to provide an even more powerful tool to simultaneously obtain both molecular information and anatomical information as well as to dramatically improve the accuracy of detection. Herein, we report a new tumor-targetable bimodal time-gated luminescence (TGL)–MRI nanoprobe for tracing cancer cells in vitro and in vivo. The nanoprobe was constructed by coating superparamagnetic Fe3O4 nanoparticles with functional silica shells that encapsulated luminescent Eu3+ complexes and were decorated with tumor-targeting molecules, folic acid (FA), on the surface. The fabricated nanoprobe possesses strong long-lived luminescence and excellent magnetic properties, as well as outstanding stability, biocompatibility and dispersibility in water. Furthermore, the nanoprobe can specifically bind to FA receptor-overexpressed cancer cells, allowing it to be accumulated in these cells. These features enable the nanoprobe to be successfully used for TGL imaging of cultured cancer cells and bimodal TGL–MR imaging of tumors in tumor-bearing mice with high sensitivity and accuracy. The research outcomes will contribute to the development of a new bimodal optical/MR imaging nanoprobe for the tracing and precise detection of cancerous cells.
研究领域:
生物医学工程
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纳米医学
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癌症研究
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2016
·
IF 8.387
Juan Li,Yuchen Tian,Dingying Shan,An Gong,Leyong Zeng,Wenzhi Ren,Lingchao Xiang,Ethan Gerhard,Jinshun Zhao,Jian Yang,Aiguo Wu
Targeted molecular imaging has attracted great attention in cancer diagnosis and treatment. However, most clinically used ultrasound contrast agents (UCAs) are non-targeted microbubbles seldom used for cancer imaging. Here, we fabricated fluorescent nanobubbles (NBs) by encapsulation of liquid tetradecafluorohexane (C 6 F 14 ) within biodegradable photoluminescent polymers (BPLPs) through an emulsion-evaporation process and conjugation of PNBL-NPY ligand for specific targeting of Y 1 receptors overexpressed in breast tumors. The developed PNBL-NPY modified NBs were uniform in size with good dispersibility and photostability, presenting good ultrasound enhancement. Further, in vitro and in vivo results indicated that the fabricated NBs exhibit high affinity and specificity to Y 1 receptor-overexpressing breast cancer cells and tumors with minimal toxicity and damage to organs. Our developed PNBL-NPY-modified NBs are novel targeted UCAs for safe, efficient and specific targeted breast cancer imaging, and may provide a new nanoplatform for early cancer diagnosis and treatment in the future.
研究领域:
医学影像
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癌症诊断
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纳米技术
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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
BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Zhikun Liu,Shining Mao,Lumei Dai,Rizhen Huang,Weiwei Hu,Chunhao Yu,Yong Yang,Guoxiu Cao,Xiaochao Huang
PARP inhibitors (PARPis) demonstrate significant potential efficacy in the clinical treatment of BRCA-mutated triple-negative breast cancer (TNBC). However, a majority of patients with TNBC do not possess BRCA mutations, and therefore cannot benefit from PARPis. Previous studies on multi-targeted molecules derived from PARPis or disruptors of RAF-RAF pathway have offered an alternative approach to develop novel anti-TNBC agents. Hence, to broaden the application of PARP inhibitors for TNBC patients with wild-type BRCA, a series of dual-targeted molecules were constructed via integrating the key pharmacophores of Olaparib (Ola) and Rigosertib into a single entity. Subsequent studies exhibited that the resulting compounds 13a – 14c obtained potential anti-proliferative activity against BRCA-defected or wild-type TNBC cells. Among them, an optimal compound 13b showed good inhibitory activity toward PARP-1, displayed approximately 34-fold higher inhibitory activity than that of Ola in MDA-MB-231 cells, and exerted multi-functional mechanisms to induce apoptosis. Moreover, 13b displayed superior antitumor efficacy (TGI, 61.3 %) than the single administration of Ola (TGI, 38.5 %), 11b (TGI, 51.8 %) or even their combined administration (TGI, 56.7 %), but did not show significant systematic toxicity. These findings suggest that 13b may serve as a potential candidate for BRCA wild-type TNBC.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
ChemNanoMat
·
2019
·Vol. 6
·期 1
·89-98
·
IF 3.431
Ming Gong,Jian Yang,Qixin Zhuang,Yongsheng Li,Jinlou Gu
Graphical A metal-organic framework (MOF)-based nanoplatform with dual-targeting functions toward cancer cells and their mitochondria is established, via a proposed phosphorylation modification strategy. With the complete coverage of targeting molecules (i. e., TPP molecules for mitochondrial targeting and FA molecules for tumoral targeting), the efficacy of photodynamic therapy is greatly improved. Due to the existence of hypoxic microenvironment, the efficacy of photodynamic therapy (PDT) is frequently weakened. As a result, targeted treatment toward oxygen-rich mitochondria is considered as a promising cancer therapy. Herein, both triphenylphosphine (TPP) and folic acid (FA) are simultaneously grafted onto nanoscale metal-organic frameworks (NMOFs) to realize dual-targeting delivery of the nanoplatforms into cancer cells and their mitochondria via the proposed phosphorylation modification strategy. A large amount of highly efficient photosensitizer of porphyrinic molecules is integrated into the NMOFs with a uniform particle size of about 65 nm. Thanks to the strong Zr−O−P bonding, a dense coverage of phosphonate-conjugating targeting molecules on NMOFs is obtained and each surficial unsaturated Zr−O cluster is adequately occupied. The resultant dual-targeting NMOFs feature high biostability and biocompatibility, as well as improved cellular uptake and mitochondrial accumulation. The PDT efficacy of these dual-targeting NMOFs is significantly improved with a low IC 50 of 0.74 μM upon 10 min light radiation, which is at least four times higher than that of non-targeting counterparts. This phosphorylation strategy would be hopeful for immobilizing a variety of biogenic groups on NMOFs to make them targetable to various specific organelles and to improve the therapy efficacy on related diseases.
研究领域:
癌症治疗
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纳米技术
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材料科学
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生物医学工程
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产品关联
DOI
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Baofu Ma,Kun Zhang,Zhen Sun,Hui Pan,Kaiguang Yang,Bo Jiang,Baofeng Zhao,Zhen Liang,Yukui Zhang,Lihua Zhang
Relatively low catalytic activity and poor targeting limit the applications of nanoceria (CeO 2 ) nanozymes in the treatment of tumors. Here, we designed a unique pushpin-like Au/CeO 2 hybrid nanozyme with high catalytic activity by combining site-selective growth and steric restriction strategies. The enhanced enzyme activity was attributed to plasmon-induced hot electrons . Furthermore, the pushpin-like structure facilitated targeting molecule modification. The nanozyme exhibited superior antitumor effects both in vitro and in vivo due to its high catalytic activity and targeting effects. Importantly, its potential mechanism of anti-tumor therapy was studied by quantitative proteomics . The reactive oxygen species (ROS) generated by folic acid-PEG thiol-Au/CeO 2 (FA-Au/CeO 2 ) caused mitochondrial and proteasomal damage in tumor cells and further evoked a response to oxidative stress and innate immunity in vivo . This study provided a spatiotemporal approach to enhance the antitumor activity of nanozymes by structural design. The designed pushpin-like Au/CeO 2 could be utilized as a multifunctional nanoplatform for in vitro and in vivo plasmon-enhanced cancer therapy with active targeting effects. Moreover, this study systematically explored the anti-tumor mechanism of the nanozyme in both cell and mouse models, promoting its translation to the clinic. Statement of significance A strategy combining the principles of site-selective growth and steric restriction was developed to prepare a unique pushpin-like Au/CeO 2 hybrid nanozyme with high catalytic activity and low steric hindrance . The hybrid nanozyme showed superior antitumor activity at both the cellular and tissue levels. Furthermore, the antitumor mechanism was investigated in terms of the differential proteins and their pathways using quantitative proteomics, thus promoting the translation of nanozymes to the clinic.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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分子生物学
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材料科学
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DOI
PubMed
高影响因子
Nano Research
·
2022
·Vol. 16
·期 5
·7148-7163
·
IF 10.269
Zhang Xiaoge,Chen Xiaomei,Zhang Peng,Li Meiting,Feng Miao,Zhang Yaqian,Cheng Lili,Tang Junjie,Xu Langtao,Liu Yadong,Liu Zhuoyin,Cao Zhong,Liu Jie
Nanomaterial-mediated phototherapy in tumor treatment has been developed rapidly in the past few years due to its noninvasive character. However, the low energy conversion efficiency and high recombination rate of the photo-triggered electron-hole pairs of single nano-agent limit the phototherapy efficiency. Herein, we constructed a novel two-dimensional nanoheterojunction MoS 2 -Ti 3 C 2 (MT), which allowed a high photothermal conversion efficiency (59.1%) as well as an effective separation of photo-triggered electron-hole pairs for reactive oxygen species (ROS) generation under single 808 nm laser irradiation. Upon the modification of the mitochondrial targeted molecule (3-proxycarboxylic) triphenyl phosphine bromide (TPP) and 4T1 cell membrane, m@MoS 2 -Ti 3 C 2 /TPP (m@MTT) could effectively target to the tumor cell and further locate to the mitochondria to amplify tumor-specific oxidative stress, which not merely effectively inhibits the local tumor growth but also induces tumor immunogenic cell death (ICD) for activating antitumor immune response. Additionally, cytosine guanine dinucleotide (CPG), as a Toll-like receptor 9 (TLR9) agonist, was further introduced to the system to boost adaptive immune responses, resulting in improved level of cytotoxic T cells as well as a decrease in the number of regulatory T cells. In vivo antitumor mechanism studies demonstrated that not only the primary and distant tumors in 4T1 bearing-tumor mice model were significantly inhibited, but also the lung metastasis of tumor was effectively suppressed. Therefore, this work revealed the ROS generation mechanism of MT nanoheterojunction and provided a novel strategy to fabricate a biomedically applicable MT nanoheterojunction for tumor treatment.
研究领域:
纳米技术
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癌症治疗
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光疗
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免疫疗法
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
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