ACS Applied Materials & Interfaces
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2023
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IF 9.5
Liang Yu,Yan Peng,Linping Jiang,Liyan Qiu
Indocyanine green (ICG) has been widely explored for the theranostics of tumors. However, ICG mainly accumulates in the liver, spleen, or kidney in addition to in tumors, causing inaccurate diagnoses and impaired therapeutic effects under NIR irradiation. Herein, a hybrid nanomicelle was constructed by integrating hypoxia-sensitive iridium(III) and ICG for precise tumor localization and photothermal therapy in sequence. In this nanomicelle, the amphiphilic iridium(III) complex (BTPH)2Ir(SA-PEG) was synthesized through the coordination substitution of hydrophobic (BTPH)2IrCl2 and hydrophilic PEGlyated succinylacetone (SA-PEG). Meanwhile, PEGlyated ICG (ICG-PEG) as a derivative of the photosensitizer ICG was also synthesized. (BTPH)2Ir(SA-PEG) and ICG-PEG were coassembled by dialysis to form the hybrid nanomicelle M-Ir-ICG. Hypoxia-sensitive fluorescence, ROS generation, and the photothermal effect of M-Ir-ICG were investigated in vitro and in vivo. The experimental results indicated that M-Ir-ICG nanomicelles could locate at the tumor site first and then perform photothermal therapy with 83.90% TIR, demonstrating great potential for clinical applications.
研究领域:
癌症研究
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纳米技术
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药学
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生物医学工程
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DOI
PubMed
高影响因子
AAPS PHARMSCITECH
·
2022
·Vol. 23
·期 6
·1-11
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IF 4.026
Meng Tingting,Li Yinghong,Tian Ying,Ma Mingxing,Shi Kequan,Shang Xuwei,Yuan Hong,Hu Fuqiang
Hypoxia is an important pathological phenomenon, and it can induce many tumor microenvironment changes, such as accumulations of intracellular lactic acid, decrease of tumor microenvironment pH value, and regulate a series of physiological and pathological processes such as adhesion, metastasis, and immune escape. Hypoxic tumor cells act as a key target for treating tumor. In this research, we designed and prepared PEG-nitroimidazole grafts, PEG-NI, and FA-PEG-NI. We first explored their physical and chemical properties to serve as a drug carrier. Then, the hypoxia-sensitive properties such as particle size changes and drug release were investigated. Finally, the tumor targeting ability was studied in vitro and in vivo , and anti-tumor capacity was determined. Both grafts showed excellent property as a nanodrug carrier and showed favorable drug encapsulation ability of sorafenib with the help of the hydrophobic chain of 6-(BOC-amino) hexyl bromide. The micelles responded to the hypoxic tumor environment with chemical and spatial structure changes leading to sensitive and fast drug release. With the modification of folic acid, FA-PEG-NI gained tumor targeting ability in vivo . FA-PEG-NI graft proved a potential targeting drug delivery system in the treatment of hypoxic hepatocellular carcinoma. Graphical Abstract
研究领域:
药理学
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肿瘤学
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分子生物学
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生物医学工程
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DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 20
·6929
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IF 4.927
Lei Yang,Mohammad Javad Afshari,Jianxian Ge,Dandan Kou,Lei Chen,Dandan Zhou,Cang Li,Shuwang Wu,Leshuai Zhang,Jianfeng Zeng,Jian Zhong,Roland H. Stauber,Mingyuan Gao
Hypoxia is a common biological condition in many malignant solid tumors that plays an imperative role in regulating tumor growth and impacting the treatment’s therapeutic effect. Therefore, the hypoxia assessment is of great significance in predicting tumor development and evaluating its prognosis. Among the plenty of existing tumor diagnosis techniques, magnetic resonance imaging (MRI) offers certain distinctive features, such as being free of ionizing radiation and providing images with a high spatial resolution. In this study, we develop a fluorescent traceable and hypoxia-sensitiveT1-weighted MRI probe (Fe3O4-Met-Cy5.5) via conjugating notable hypoxia-sensitive metronidazole moiety and Cy5.5 dye with ultrasmall iron oxide (Fe3O4) nanoparticles. The results of in vitro and in vivo experiments show that Fe3O4-Met-Cy5.5 has excellent performance in relaxivity, biocompatibility, and hypoxia specificity. More importantly, the obvious signal enhancement in hypoxic areas indicates that the probe has great feasibility for sensing tumor hypoxia viaT1-weighted MRI. These promising results may unlock the potential of Fe3O4nanoparticles asT1-weighted contrast agents for the development of clinical hypoxia probes.Keywords:tumor hypoxia;ultrasmall iron oxide nanoparticles;magnetic resonance imaging;metronidazole
研究领域:
医学影像
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纳米技术
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肿瘤学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
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IF 7.727
Xinghui Si,Sheng Ma,Yudi Xu,Dawei Zhang,Na Shen,Haiyang Yu,Yu Zhang,Wantong Song,Zhaohui Tang,Xuesi Chen
As the most common malignancy in women, breast cancer causes >40,000 deaths annually. Ribonuclease A (RNase), a new anti-cancer agent, has attracted intense interest due to its high efficacy and specificity. However, RNase suffers from instability, a short half-life in the circulation and poor membrane penetration. To overcome these challenges, we designed a supramolecular nanogel for the cytosolic delivery of RNase. The nanogels were fabricated using host–guest interactions between azobenzene (Azo) and β-cyclodextrin (βCD) conjugated to poly (L-glutamic acid)- graft -poly (ethylene glycol) methyl ether (PLG- g -mPEG). RNase could be loaded inside the nanogels in mild aqueous conditions. Following optimization, the RNase-loading content and efficiency of the nanogel were 23.5 wt% and 50.4%, respectively. In the presence of nitroreductase (NTR), the cross-linking point between Azo and βCD was destroyed due to the conformation transition of Azo, ensuring the hypoxia-sensitive release of cargo from the nanogels in tumors in which NTR is overexpressed. In vitro release profiles revealed that 75.0% of the RNase was released under hypoxic conditions in 72 h, whilst only 19.7% was released under normoxic conditions. Cytotoxicity assays showed that the RNase-loaded nanogels (nano-RNase) were more efficient in inhibiting the proliferation of 4T1 cells than free RNase. In vivo studies showed 68.7% tumor suppression rates (TSR %) in the nano-RNase treated group, whilst free RNase treatment led to a lack of tumor inhibition. To further enhance the hypoxia status of tumors, we combined nano-RNase with a nanoformulation of vascular disrupting agents PLG- g -mPEG/combretastatinA4 (nano-CA4) and obtained a TSR of 91.7%. The hypoxia-sensitive supramolecular nanogels provided a versatile platform for the delivery of RNase, highlighting its applicability for cancer therapy.
研究领域:
药学
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癌症研究
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纳米技术
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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
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Kunpeng Lin,Shaochen Wang,Shuling Yu,Wen Si,Miaojie Yang,Ningning Xu,Yu Liu,Yan Zheng,Shuang Zhao,Jiahua Shi,Jintao Yuan
Porphyrins are popular photosensitizers for photodynamic therapy of diseases. However, the poor water solution and short absorption wavelengths of porphyrins limit their clinical application. In this work, a novel worm-like porphyrin covalent organic framework (Por-COF) with excellent dispersibility and near-infrared absorption was prepared via a facile method. First, a pH-responsive macromolecule was prepared using Schiff base bonds between porphyrin and terephthalaldehyde, and the spatial arrangement of macromolecules was controlled to prepare Por-COF. Second, the hypoxia-responsive drug tirapazamine (TPZ) and tumor-targeted hyaluronic acid (HA) were loaded to Por-COF through the electrostatic effect to prepare a multifunction nanomedicine (Por-COF@TPZ/HA) that could simultaneously produce abundant reactive oxygen species and high temperature via808 nm laser irradiation. TPZ was cascaded for the synergistic therapy of cancers. In vitro cytotoxicity showed that the inhibition rate of cell activity in the Por-COF@TPZ/HA + Laser group was 1.2 times higher than that in the Por-COF/HA + Laser group. In vivo experiments also demonstrated that the aggravated tumor hypoxia caused by photodynamic therapy could activate TPZ to achieve high-efficiency chemotherapy. Combined photodynamic–photothermal therapy and chemotherapy had an outstanding synergistic effect. This work provides a promising method for Por-COF preparation and a feasible strategy for the synergistic therapy of cancers.
研究领域:
化学
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材料科学
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肿瘤学
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药学
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DOI
PubMed
高影响因子
Nanoscale
·
2023
·Vol. 15
·期 27
·11625-11646
·
IF 6.7
Kai Wang,Wentao Zhou,Xiangyu Jin,Xuwei Shang,Xiaomei Wu,Lijuan Wen,Sufen Li,Yiling Hong,Jia Ke,Yichong Xu,Hong Yuan,Fuqiang Hu
Ischemic stroke is characterized by high morbidity, disability, and mortality. Unfortunately, the only FDA-approved pharmacological thrombolytic, alteplase, has a narrow therapeutic window of only 4.5 h. Other drugs like neuroprotective agents have not been clinically used because of their low efficacy. To improve the efficacy of neuroprotective agents and the effectiveness of rescue therapies for hyperacute ischemic stroke, we investigated and verified the variation trends of the blood–brain barrier (BBB) permeability and regional cerebral blood flow over 24 h in rats that had ischemic strokes. Hypoperfusion and the biphasic increase of BBB permeability are still the main limiting factors for lesion-specific drug distribution and drug brain penetration. Herein, the nitric oxide donor hydroxyurea (HYD) was reported to downregulate the expression of tight junction proteins and upregulate intracellular nitric oxide content in the brain microvascular endothelial cells subjected to oxygen–glucose deprivation, which was shown to facilitate the transport of liposomes across brain endothelial monolayer in an in vitro model. HYD also increased the BBB permeability and promoted microcirculation in the hyperacute phase of stroke. The neutrophil-like cell-membrane-fusogenic hypoxia-sensitive liposomes exhibited excellent performance in targeting the inflamed brain microvascular endothelial cells, enhancing cell association, and promoting rapid hypoxic-responsive release in the hypoxic microenvironment. Overall, the combined HYD and hypoxia-sensitive liposome dosing regimen effectively decreased the cerebral infarction volume and relieved neurological dysfunction in rats that had ischemic strokes; these therapies were involved in the anti-oxidative stress effect and the neurotrophic effect mediated by macrophage migration inhibitory factor.
研究领域:
神经科学
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药理学
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治疗学
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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
BIOMACROMOLECULES
·
2021
·
IF 6.988
Tingjie Yin,Xuxin Chu,Jiejie Cheng,Jinlai Liang,Jianping Zhou,Meirong Huo
A hypoxia-sensitive zwitterionic vehicle, DHigh-PEI-(A+P), with the ability for antifouling-mediated, stable biotransport and a photodynamic therapy (PDT)-sensitized hypoxic response for spatiotemporal controlled drug release, was developed for the tumor-specific delivery of chemotherapeutics and biomacromolecules. The amphiphilic DHigh-PEI-(A+P) was constructed from a betaine monomer (DMAAPS), a photosensitizer (PpIX), and an azobenzene-4,4′-dicarboxylic acid-modified polyethylenimine. Herein paclitaxel (PTX) was selected as a common model drug to verify the functions of the designed polymer. First, DHigh-PEI-(A+P) was demonstrated to spontaneously coassemble with PTX in aqueous solution with high drug loading (>35%). The desirable antifouling ability of DHigh-PEI-(A+P) was independently verified by efficient 4T1 endocytosis in serum alongside systemic tumor targeting. Furthermore, PpIX-mediated PDT was verified to aggravate and homogenize a hypoxic microenvironment at the cell and tissue levels for a sharp responsive disassembly of DHigh-PEI-(A+P) and thus a robust drug release in a well-controlled manner. As a result, DHigh-PEI-(A+P) amplified the therapeutic outcome of PTX on orthotopic 4T1 mouse models with minimal collateral damage. We proposed that DHigh-PEI-(A+P) may serve as a tailor-designed universal vehicle for the tumor-specific delivery of drugs with distinct physicochemical properties.
研究领域:
癌症治疗
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药物递送系统
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生物医学工程
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纳米技术
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药学科学
✓ 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）