Journal of Materials Chemistry B
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2022
·Vol. 10
·期 22
·4306-4320
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IF 7.571
Jie Zhou,Qianwen Yin,Shengnan Li,Ruhe Yang,Rui Lou,Yiwen Sun,Bin Du
The poor penetration into deep tumor tissues of nanomedicines could not inhibit the production of lactic acid by deep tumor glycolysis, which leads to the accumulation of lactic acid and promotes tumor metastasis. In order to increase tumor penetration, it remains challenging to avoid tumor metastasis by the direct degradation of the extracellular matrix (ECM). Herein, in order to increase tumor penetration, a nano-platform, which can reduce extracellular matrix (ECM) production, and inhibit the glycolysis of deep tumors by releasing ethylenediaminetetraacetic acid (EDTA) is reported. In this design, EDTA and indocyanine green (ICG) are encapsulated in the liposome by a thin-film hydration method, and folic acid (FA) and the polyethyleneimine polymer (FA-PEI) are applied to coat the surface of liposomes through electrostatic interactions, and the FA-EDTA/ICG-Lip nanoparticles are obtained. FA-EDTA/ICG-Lip NPs can release EDTA and ICG in lysosomes (pH 4.5) to reduce ECM production by down-regulating transforming growth factor β (TGF-β) and activating an immune response by inducing tumor cell immunogenic cell death (ICD), respectively. Simultaneously, EDTA inhibits glycolysis of deep tumors by chelating Mg2+. By avoiding tumor metastasis, the strategy of indirectly reducing ECM production is demonstrated to enhance tumor penetration and inhibit deep tumor glycolysis.
研究领域:
肿瘤学
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纳米医学
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免疫学
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DOI
PubMed
高影响因子
Pharmaceutics
·
2023
·Vol. 15
·期 4
·1217
·
IF 5.4
Tushuai Li,Yue Gu,Lisha Yu,Shenglong Zhu,Jie Zhang,Yongquan Chen
Tumor microenvironment (TME)-induced nanocatalytic therapy is a trending strategy for tumor-targeting therapy, but the low catalytic efficiency remains to limit its therapeutic effect. The single-atom catalysts (SACs) appear as a novel type of nanozymes that possesses incredible catalytic activity. Here, we developed PEGylated manganese/iron-based SACs (Mn/Fe PSACs) by coordinating single-atom Mn/Fe to nitrogen atoms in hollow zeolitic imidazolate frameworks (ZIFs). Mn/Fe PSACs catalyze cellular hydrogen peroxide (H2O2) converting to hydroxyl radical (•OH) through a Fenton-like reaction; it also enhances the decomposition of H2O2to O2that continuously converts to cytotoxic superoxide ion (•O2−) via oxidase-like activity. Mn/Fe PSACs can reduce the depletion of reactive oxygen species (ROS) by consuming glutathione (GSH). Here, we demonstrated the Mn/Fe PSACs-mediated synergistic antitumor efficacy among in vitro and in vivo experiments. This study proposes new promising single-atom nanozymes with highly efficient biocatalytic sites and synergistic therapeutic effects, which will give birth to abundant inspirations in ROS-related biological applications in broad biomedical fields.Keywords:tumor microenvironment;single-atom catalysts;reactive oxygen species;synergistic antitumor
研究领域:
纳米技术
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癌症生物学
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生物医学工程
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DOI
PubMed
高影响因子
Acta Biomaterialia
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2016
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IF 6.008
Zhoujiang Chen,Nan He,Maohua Chen,Long Zhao,Xiaohong Li
Micelles self-assembled from drug-conjugated polymers indicate advantages in alleviating the premature release before reaching the intended site. Hyaluronic acid (HA) is known to specifically bind with a transmembrane glycoprotein CD44 , overexpressed in many types of cancerous cells, and can also be served as micelle carriers. However, an excess amount of drug conjugation to HA backbone may be detrimental to the receptor-mediated cellular uptake. Up to now, the effect of conjugation densities of drugs has never been determined on the physical properties and biological performance of resulting micelles. In the current study, camptothecin (CPT) was conjugated on HA through 3,3′-dithiodipropionic acid to self-assemble into reduction-sensitive micelles. The substitution degrees of CPT on HA backbone were tuned from around 4–20%, to clarify the effects on the cellular uptake efficiency and cytotoxicities of micelles, as well as the tumor accumulation and antitumor efficacy. The CPT substitution degree of around 15% on HA resulted in micelles with a higher cytotoxicity to 4T1 cells and achieved a better balance between the cellular uptake and reduction-triggered drug release, compared with other micelles. In contrast to a fast kidney clearance and an even distribution in major organs after intravenous injection of free CPT, the optimized micelles were accumulated in tumors, livers and lungs. The micelle content indicated a significant decrease in livers after 24 h, while that in tumors displayed a significant increase to 4.9% of the injection dose. The tumor accumulation of micelles led to strong tumor suppression with minimal systemic toxicity. The in situ tumor inhibition and the accumulation of micelles in liver and lungs inhibited tumor metastasis to these tissues. It demonstrates a feasible strategy to develop drug-HA conjugate micelles with a concise and tunable structure for tumor targeting and reduction-triggered release. Statement of Significance Hyaluronic acid (HA) can be served as micelle carriers and targeting ligands to tumor cells. However, the effects of drug conjugation densities on the physical profile and biological performance of resulting micelles have never been investigated. In the current study, camptothecin is conjugated on HA with reduction-sensitive linkers, and the substitution degrees of camptothecin on HA backbone vary from around 4–20%. The micelles with a substitution degree of around 15% achieve a better balance between the cellular uptake and reduction-triggered drug release and a higher cytotoxicity than others. It demonstrates a feasible strategy to develop drug-HA conjugate micelles with a concise and tunable structure for tumor targeting and reduction-triggered release.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2021
·
IF 7.328
Zechun Dang,Jizheng Sun,Jiaqi Fan,Jinqi Li,Xinlei Li,Tongsheng Chen
Zinc oxide (ZnO) nanostructures have been widely studied in biomedical fields due to their special properties. In recent years, ZnO spherical nanoparticles (SNPs) with nano-size as an anti-tumor agent have been widely concerned. While the effects of the non-spherical shaped ZnO nanoparticles on tumor cell death have been rarely reported. Here, we prepared ZnO spiky nanoparticles (SPNPs) as the research subject. We found that the SPNPs showed superiority in killing tumor cells. To be specific, SPNPs presented a long-term cytotoxicity effect on killing tumor cells, as plenty of SPNPs retained on the cell plasma membrane's exterior and still showed toxicity effect on tumor cells after co-incubation multiple times. Moreover, compared to SNPs, it was encouraging that SPNPs still showed stronger cytotoxicity in both simulated circulatory systems of tumor cells and 3D tumor cell spheroids. The stronger toxicity against tumor cells suggested that ZnO SPNPs have more advantages on killing tumor cells as a promising nanomedicine.
研究领域:
生物医学工程
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纳米技术
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癌症研究
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Rui Chang,Rongrong Fu,Yujiao Huang,Jibing Zhang,Changshun Feng,Rui Wang,Hui Yan,Guangyong Li,Xiaohong Chu,Fengjiao Yuan,Dianlong Jia,Jun Li
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) constitutes a promising antitumor drug, tumor resistance to TRAIL has become a major obstacle in its clinical application. Mitomycin C (MMC) is an effective TRAIL-resistant tumor sensitizer, which indicates a potential utility of combination therapy. However, the efficacy of this combination therapy is limited owing to its short half-life and the cumulative toxicity of MMC. To address these issues, we successfully developed a multifunctional liposome (MTLPs) with human TRAIL protein on the surface and MMC encapsulated in the internal aqueous phase to codeliver TRAIL and MMC. MTLPs are uniform spherical particles that exhibit efficient cellular uptake by HT-29 TRAIL-resistant tumor cells, thereby inducing a stronger killing effect compared with control groups. In vivo assays revealed that MTLPs efficiently accumulated in tumors and safely achieved 97.8% tumor suppression via the synergistic effect of TRAIL and MMC in an HT-29 tumor xenograft model while ensuring biosafety. These results suggest that the liposomal codelivery of TRAIL and MMC provides a novel approach to overcome TRAIL-resistant tumors.
研究领域:
药理学
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肿瘤学
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药物递送系统
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生物技术
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Jialuo Ai,Yixuan Huang,Zhaoyi Yin,Yingshan Deng,Ling Yan,Jingwen Liao,Guoyan Liang,Chong Chen,Yunbing Chang,Cairong Xiao,Jiale Zhou,Zurong Zhu,Chengli Liu,Zhuo Jiang,Chengyun Ning,Zhengao Wang
Combining the detection of tumor protein markers with the capture of circulating tumor cells (CTCs) represents an ultra-promising approach for early tumor detection. However, current methodologies have not yet achieved the necessary low detection limits and efficient capture. Here, we introduced a novel polypyrrole nanotentacles sensing platform featuring anemone-like structures capable of simultaneously detecting protein biomarkers and capturing CTCs. The incorporation of nanotentacles significantly enhanced the electrode surface area, providing abundant active sites for antibody binding. This enhancement allowed detecting nucleus matrix protein22 (NMP22) and bladder tumor antigen (BTA) with 2.39 and 3.12 pg/mL detection limit, respectively. Furthermore, our developed sensing platform effectively captured MCF-7 cells in blood samples with a detection limit of fewer than 10 cells/mL, attributed to the synergistic multivalent binding facilitated by the specific recognition antibodies and the positive charge on the nanotentacles surface. This sensing platform demonstrated excellent detection capabilities and outstanding capture efficiency, offering a simple, accurate, and efficient strategy for early tumor detection. This article is protected by copyright. All rights reserved
研究领域:
生物医学工程
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材料科学
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肿瘤学
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分析化学
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产品关联
DOI
PubMed
高影响因子
Nano Today
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2024
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IF 13.2
Liting Chen,Chen Xu,Hainan Xu,Hongyu Liu,Zihan Ma,Jiahao Liu,Xiaoyu Gao,Wei Lv,Xinze Du,Xiao Zhao,Jing Shi,Keman Cheng,Funan Liu
Oncolytic virus therapy for brain tumors has achieved breakthrough progress in clinical applications, yet its potential is severely constrained by the mode of administration-direct intratumoral injection into the cranial cavity. Other administration routes face rapid clearance by neutralizing antibodies and obstacles posed by the blood-brain barrier. Herein, we engineered the oncolytic herpes simplex virus type 2 (OH2) with surface modifications of polyethylene glycol (PEG) and rabies virus glycoprotein 29 (RVG29, a BBB-penetrating peptide from the rabies virus), to form OH2-PEG-RVG. OH2-PEG-RVG could efficiently traversed the blood-brain barrier even in BALB/c mice with pre-existing anti-OH2 antibodies, leading to the accumulation of OH2 in the brain. More importantly, OH2-PEG-RVG maintained blood-brain barrier integrity without causing pathological changes or behavioral abnormalities in mice. Furthermore, OH2-PEG-RVG effectively inhibited brain tumor growth, transforming immunologically "cold" tumors into "hot" tumors, inducing a robust anti-tumor immune response, and prolonging the survival of the mice. These findings underscore the potential of OH2-PEG-RVG as a multifaceted therapeutic strategy for effective brain tumor treatment, offering insights into addressing blood-brain barrier limitations.
研究领域:
肿瘤学
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神经科学
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病毒学
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免疫疗法
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2024
·
IF 13.3
Zhihuang Zhang,Yan Peng,Liyan Qiu
The enrichment of M2-phenotype tumor-associated macrophages (TAMs) is the main factor to create an immunosuppressive microenvironment, which seriously attenuates antitumor treatment. Herein, we explored the capability of rigid nanoparticles to reprogram TAMs to the M1-like phenotype via mechanical force. We designed and synthesized amphiphilic copolymer PLA- b -PItEG initiated by the HO-Pd(II) complex. In contrast to polyethylene glycol, the hydrophilic PItEG segments have a helical conformation, which endows the self-assembled PLA- b -PItEG nanoparticles with stiff surface characteristics of higher Young’s modulus and hydrophobicity. The rigid nanoparticles displayed strong interaction with TAMs to produce greater deformation of cell membrane and activated mechanosensitive potassium ion channel. Consequently, rigid nanoparticles exerted a positive effect on the proinflammatory polarization of TAMs. The expression level of CD86, a typical M1 macrophage marker, was increased by 60% compared with that in the soft PEG-NP group while CD206, a typical M2 macrophage marker, was decreased. Furthermore, several M1-related cytokines such as TNF-α, IL12p40, IL-6 and IL-1β were upregulated. In vitro and in vivo immune responses triggered by rigid nanoparticles could significantly inhibit B16F10 tumor growth with 71.44% tumor inhibitory rate. This study offers new insight into the use of mechanical forces for tumor immunotherapy.
研究领域:
纳米技术
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免疫治疗
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癌症研究
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生物医学工程
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Qi Meng,Xiao Tan,Bi Wu,Siyan Zhang,Yuangang Zu,Shougang Jiang
The decoctions of sunflower ( Helianthus annuus L. HAL) stalk pith have been used to treat advanced cancer, and polysaccharide of sunflower stalk pith (HSPP) was key ingredient of the decoctions. To forage specially structured HSPP with anti-tumor effects and to uncover its mechanisms of anticancer activity, syngeneic mouse model of lung carcinoma metastasis was established and the HSPP was found to contain long-chain fatty acid. Encouragingly, the mean survival of the polysaccharide group (47.3 ± 12.8 d) and its sub-fractions group HSPP-4 (50.7 ± 13.0 d) was significantly increased compared with control group (38.7 ± 12.7 d) or positive control group (41.8 ± 13.4 d), ( n = 20, P < 0.01 vs. the control group or positive control group). Furthermore, the HSPP exerted inhibitory effects on the tumor cells' metastasis. Eventually, it is postulated that the polysaccharide could inhibit tumor proliferation and metastasis by reduction of TNF-α from the macrophage.
研究领域:
药理学
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肿瘤学
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植物化学
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产品关联
DOI
PubMed
高影响因子
Nature Biomedical Engineering
·
2022
·Vol. 6
·期 7
·898-909
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IF 29.234
Yue Yale,Xu Jiaqi,Li Yao,Cheng Keman,Feng Qingqing,Ma Xiaotu,Ma Nana,Zhang Tianjiao,Wang Xinwei,Zhao Xiao,Nie Guangjun
The complex gastrointestinal environment and the intestinal epithelial barrier constrain the design and effectiveness of orally administered tumour vaccines. Here we show that outer membrane vesicles (OMVs) fused to a tumour antigen and produced in the intestine by ingested genetically engineered bacteria function as effective tumour vaccines in mice. We modified Escherichia coli to express, under the control of a promoter induced by the monosaccharide arabinose, a specific tumour antigen fused with the protein cytolysin A on the surface of OMVs released by the commensal bacteria. In mice, oral administration of arabinose and the genetically engineered E. coli led to the production of OMVs that crossed the intestinal epithelium into the lamina propria, where they stimulated dendritic cell maturation. In a mouse model of pulmonary metastatic melanoma and in mice bearing subcutaneous colon tumours, the antigen-bearing OMVs inhibited tumour growth and protected the animals against tumour re-challenge. The in situ production of OMVs by genetically modified commensal bacteria for the delivery of stimulatory molecules could be leveraged for the development of other oral vaccines and therapeutics.
研究领域:
癌症生物学
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免疫学
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分子生物学
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生物技术
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2022
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IF 10.383
Qingfei Zhang,Gaizhen Kuang,Yunru Yu,Xiaoya Ding,Haozhen Ren,Weijian Sun,Yuanjin Zhao
Chemo-immunotherapy shows promising antitumor therapeutic outcomes for many primary cancers. Research in this area has been focusing on developing an ideal formula that enables the potent efficacy of chemo-immunotherapy in combating various cancers with reduced systemic toxicity. Herein, we present novel hierarchical hydrogel microparticles (MDDP) delivering oxaliplatin and NLG919 nanoprodrugs for local chemo-immunotherapy with desired features. The oxaliplatin prodrug and NLG919 were efficiently loaded in the dual-drug polymeric nanoparticles (DDP NPs), which were further encapsulated into a MDDP by using microfluidic technology. When delivered to the tumor site, the DDP NPs will be sustainedly released from the MDDP and retained locally to reduce systemic toxicity. After being endocytosed by cancer cells, the cytotoxic oxaliplatin and NLG919 could be successfully triggered to release from DDP NPs in a chain-shattering manner, leading to the immunogenic cell death (ICD) of tumor cells and the suppression of intratumoral immunosuppressive Tregs, respectively. With the assistance of an immune modulator, the chemotherapeutics-induced ICD could trigger robust systemic antitumor immune responses, presenting superior synergistic antitumor efficacies. Thus, the hierarchical microparticles could substantially inhibit the growth of mouse subcutaneous colorectal tumors, breast tumors, and colorectal tumors with large initial sizes via synergized chemo-immunotherapy, showing great potential in the practical clinical application of oncotherapy.
研究领域:
肿瘤学
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药学
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免疫学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Fangyuan Guo,Yunlong Jiao,Yinzhou Du,Shuai Luo,Weiyong Hong,Qiafan Fu,Aiqin Li,Guoping Wang,Gensheng Yang
Efficient drug loading, tumor targeting, intratumoral penetration, and cellular uptake are the main factors affecting the effectiveness of drug delivery systems in oncotherapy. Based on the tumor microenvironment, we proposed to develop Curcumin (Cur)-loaded matrix metalloproteinase (MMP)-responsive nanoparticles (Cur-P-NPs) by static electricity, to enhance tumor targeting, cellular uptake, and drug loading efficiency. These nanoparticles combine the properties of both PEG-peptides (cleaved peptide + penetrating peptide) and star -shaped polyester (DPE-PCL) nanoparticles. Cur-P-NPs displayed good entrapment efficiency, drug loading and biocompatibility. Additionally, they showed an enhanced release rate, cellular uptake, and anti-proliferative activity by activating peptides under the simulated tumor microenvironment. Furthermore, intraperitoneal injection of losartan (LST) successfully enhanced intratumoral drug penetration by collagen I degradation. In vivo studies based on the systematic administration of the synergistic LST + Cur-P-NPs combination to mice confirmed that combined antitumor therapy with LST and Cur-P-NPs could further improve intratumor distribution, enhance anticancer efficacy, and reduce the toxicity and side effects. Therefore, LST + Cur-P-NPs represent a new and efficient system for clinical oncotherapy.
研究领域:
药学
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肿瘤学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）