ANALYTICA CHIMICA ACTA
·
2021
·
IF 6.558
Qi Liu,Shushu Ding,Rui Gao,Guoyue Shi,Anwei Zhu
ATP-sensitive potassium (K ATP ) channels couple intracellular metabolism to the electrical activity by regulating K + flux across the plasma membrane, thus playing an important role in both normal and pathophysiology. To understand the mechanism of ATP regulating biological ion channels, developing an ATP-responsive artificial nanochannel is an appealing but challenging topic because K ATP channel is a heteromultimer of two subunits (potassium channel subunit (Kir6.x) and sulfonylurea receptor (SUR)) and exhibit dynamic functions with adjustability and reversibility. Inspired by the structure of K ATP channels, we designed a smart copolymer modified nanochannel that may address the challenge. In the tricomponent poly( N -isopropylacrylamide) (PNIPAAm, PNI)-based copolymer system, phenylthiourea was used to bind the phosphate units of nucleotides and phenylboronic acid was introduced to combine the pentose ring of the nucleoside unit. Besides, a –COOH group with electron-withdrawing property was added into the phenylthiourea units, which may promote the hydrogen-bond-donating ability of thiourea . Specially, the smart copolymer not only provided static binding sites for recognition but also translated the recognition of ATP into their dynamic conformational transitions by changing the hydrogen-bonding environments surrounding PNIPAAm chains, thus achieving the gating function of nanochannel, which resembled the integration and coordination of Kir6.x and SUR units in active K ATP . The ATP-regulated ion channel exhibited excellent stability and reversibility. This study is the first example showing how to learn from nature to assemble the ATP-responsive artificial nanochannel and demonstrate the possible mechanism of ATP gating.
研究领域:
生物化学
·
材料科学
·
分子生物学
✓ 已验证
DOI
高影响因子
Polymer Chemistry
·
2021
·Vol. 12
·期 8
·1125-1135
·
IF 5.582
Yanfen Jiang,Shuqi Dong,Guoyang Qin,Li Liu,Hanying Zhao
This study reports the facile synthesis of a phenylboronic acid-functionalized block copolymer containing tertiary sulfoniums via the combination of reversible addition–fragmentation chain transfer polymerization of a methionine-derived methacrylate monomer and the alkylation of thioether. The block copolymer self-assembled to form positively charged spherical micelles in aqueous media. Because of the deboronation and subsequent benzyl 1,6-elimination reaction in the presence of H2O2, the micelles displayed an oxidation-responsive feature. Triggered by H2O2, the micelles underwent an expansion, and the surface charge decreased due to the transformation of cationic sulfoniums to neutral sulfurs. Moreover, the micelles can interact with adenosine triphosphate (ATP) via the formation of reversible boronates and electrostatic interactions. In the presence of ATP, the block copolymer micelles spontaneously contracted to small aggregates of ATP/copolymer complexes. Taking advantage of the cationic sulfoniums, the block copolymer co-assembled with negatively charged bovine serum albumin (BSA) to fabricate protein-entrapped biohybrid micelles, driven by multiple electrostatic interactions. BSA in the micelles retained 94% of the native BSA bioactivity. Triggered by H2O2, the BSA-entrapped micelles underwent destruction because of the charge conversion of sulfonium cations to neutral sulfurs. The BSA-entrapped micelles have good biocompatibility and demonstrate an H2O2 and ATP dual-responsive release profile.
研究领域:
高分子化学
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生物材料
·
药物递送
✓ 已验证
DOI
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 9
·1-10
·
IF 5.833
Chen Xi-Xi,Hou Mei-Jia,Mao Guo-Jiang,Wang Wen-Xin,Xu Fen,Li Yongfei,Li Chun-Yan
A near-infrared (NIR) fluorescence nanoprobe named RhI-DOX@ZIF-90 has been synthesized by wrapping the guest molecule (RhI and DOX) into ZIF-90 framework. The nanoprobe itself is non-fluorescent and the drug (DOX) is inactive. Upon the addition of ATP, the structure of RhI-DOX@ZIF-90 is degraded. The fluorescence of RhI is recovered and DOX is released. The nanoprobe can detect ATP with high sensitivity and selectivity. There is good linear relationship between the nanoprobe and ATP concentration from 0.25 to 10 mM and the detection limit is 0.10 mM. The nanoprobe has the ability to monitor the change of ATP level in living cells and DOX is released inducing apoptosis of cancer cells. RhI-DOX@ZIF-90 is capable of targeting mitochondria, which provides a basis for improving the efficiency of drug delivery by mitochondrial administration. In particular, the nanoprobe is preferentially accumulated in the tumor sites and detect ATP in tumor mice by fluorescence imaging using near-infrared fluorescence. At the same time, DOX can be released accurately in tumor sites and have good anti-tumor efficiency. So, this nanoprobe is a reliable tool to realize early diagnosis of cancer and improve effect of anticancer drug. Graphical abstract
研究领域:
生物医学工程
·
纳米医学
·
肿瘤学
✓ 已验证
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Yuqing Tong,Wei Jiang,Jinyu Li,Peng Teng,Lulu Wei,Huae Xu,Xiqun Jiang,Yong Hu
The inefficient delivery of drugs into tumor cells by nanodrugs remains a major challenge in enhancing drug utilization. Herein, inspired by the mechanism used by cytotoxic T lymphocytes (CTL) to efficiently deliver granzyme into tumor cells by recognizing tumor cells, damaging membranes and facilitating drug entry into cells, the biomimetic nanodrug (Mem-Poly/CaO 2 /Dox) was developed. This nanodrug utilized acid and ATP dual responsiveness to perforate tumor cell membrane and enhance directly intracellular drug delivery. Upon administration, Mem-Poly/CaO 2 /Dox recognized homologous tumor cells through its surface-coated tumor cell membrane. Then, Mem-Poly/CaO 2 /Dox responded to acidic tumor environment and rapidly released calcium peroxide nanoparticles (CaO 2 ). The released CaO 2 adhered to the tumor cell membrane and subsequently generated hydrogen peroxide (H 2 O 2 ) in situ within acidic tumor microenvironment, causing membrane injured and forming micro holes. This membrane disruption led to ATP leakage from tumor cells, further triggering the disassembly of the responsive polymer and Dox release. The released Dox then directly entered tumor cells through the damaged membrane and induced cell death through apoptosis and ferroptosis. Experimental results demonstrated that Mem-Poly/CaO 2 /Dox achieved significantly higher drug delivery efficiency than conventional nanodrugs, which primarily rely on the endocytosis-lysosomal escape pathway. By simulating the granzyme delivery mechanism of CTL, this highly efficient strategy breaches biological barriers of the cell membrane and offers a promising strategy to improve delivery efficiency and anti-tumor potency of chemotherapeutics.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
高影响因子
Acta Biomaterialia
·
2022
·
IF 10.633
Yuqin Zeng,Can Zhang,Dou Du,Ya Li,Lu Sun,Yuanyuan Han,Xiaoxiao He,Jianwu Dai,Liyang Shi
Metal-organic framework (MOF) is an exciting class of porous biomaterials that have been considered as a carrier to store and deliver therapeutic drugs. However, similar to other nanomaterials , the application of MOF in clinical settings is still limited because of premature diffusion of their payloads and tissue off-targeting behavior. To overcome these challenges, we designed an MOF-based hydrogel with structurally dynamic properties, i.e. , self-healing and shear-thinning, as an injectable localized drug delivery platform. The drug-encapsulating MOF hydrogel is formed through a dynamic coordination bond cross-linkage between a doxorubicin-loaded MOF ( [email protected] ) particle and a homemade bisphosphonate-modified hyaluronic acid (HA-BP) polymeric binder. The HA-BP· [email protected] hydrogel demonstrates pH- and ATP-responsive drug release characteristic and efficiently kills cancer cells in vitro . The animal experiments reveal that the HA-BP· [email protected] hydrogel has enhanced capability in terms of tumor growth suppression as compared to the [email protected] group, which can be attributed to drug localization in hydrogel superstructure and sustained release at the tumor site. The presented injectable dynamic MOF-based hydrogel is a promising in vivo localized drug delivery system for cancer treatment. Herein, we report the self-healing and shear-thinning of MOF-based drug carrier cross-linked by coordinate bonds for the first time and provide new insights and a facile chemical strategy for designing and fabricating MOF-based biomaterials by using bisphosphonate-zinc interaction. Statement of significance Bisphosphonate-zinc interaction is a facile chemical strategy to cross-link metal-organic framework (MOF)-based hydrogel. The presented MOF-based hydrogel demonstrates structurally dynamic properties, including smooth injectability, self-healing, and shear-thinning. The developed MOF-based hydrogel possesses pH- and ATP-responsive drug release characteristic and kills cancer cells in vitro efficiently. The dynamic MOF-based hydrogel shows enhanced in vivo anticancer activity as compared to pure MOF particles. Self-healing and shear-thinning of metal-ligand cross-linked MOF-based drug delivery system are reported for the first time, thus providing new insights for the design and fabrication of MOF-based biomaterials.
研究领域:
材料科学
·
生物医学工程
·
药学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2016
·Vol. 4
·期 21
·3832-3841
·
IF 4.872
Guan-Hai Wang,Guo-Liang Huang,Yi Zhao,Xing-Xiang Pu,Tong Li,Jun-Jie Deng,Jian-Tao Lin
Stimuli-responsive nanocarriers for anticancer drug and gene co-delivery are a promising strategy in cancer therapy due to their combination of chemotherapy and gene therapy. In this work, we developed a facile and effective method to fabricate stimuli-responsive nanocarriers for anticancer drug and gene co-delivery based on complexes of polyethylenimine (PEI) with an adenosine triphosphate (ATP) responsive aptamer duplex (ARAD). No chemical reactions or complex modifications were used in the construction processes. In this system, Doxorubicin-loaded aptamer duplex and plasmid DNA (p53) can be bound by PEI by electronic interactions to form stable complexes which effectively protect the aptamer and p53 from DNase degradation. The intercalated Dox can be released on-demand by a structural change in the aptamer duplex in an ATP-rich environment. The morphology and average size of the nanocarriers were characterized by zeta potential and transmission electron microscopy (TEM). The nanocarriers exhibit lower cell toxicity in HeLa cell lines relative to PEI. RT-PCR and Western blot analysis confirmed that p53 could be effectively delivered and expressed in HeLa cells by PEI/ARAD/p53 complexes. Moreover, the apoptosis percentage of HeLa cells treated with PEI/ARAD/Dox/p53 complex increased to 40.8%, compared to 24.7% for PEI/ARAD/Dox complex and 11.5% for PEI/ARAD/p53, respectively. The result demonstrated that the combinatorial delivery of Dox and p53 by nanocarriers could induce synergistic actions and lead to effective cancer cell apoptosis.
研究领域:
癌症治疗
·
药物递送系统
·
分子生物学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2020
·Vol. 14
·期 1
·222-231
·
IF 8.183
Zhu Huimin,Cao Guodong,Fu Yike,Fang Chao,Chu Qiang,Li Xiang,Wu Yulian,Han Gaorong
Multidrug resistance (MDR) restricts chemotherapy efficacy due to P-glycoprotein (P-gp) mediated drug efflux, whereas current approaches to suppressing P-gp expression suffer from intrinsic challenges, such as low transfection, high toxicity and poor specificity. Here, hollow ferric-tannic acid complex nanocapsules (HFe-TA), which can be effectively degraded by the reaction with adenosine triphosphate (ATP), are synthesized for the delivery of glucose oxidase (GOx) and doxorubicin (DOX) for tumor treatment. The findings indicate that the intracellular ATP is significantly decreased due to the combined effect of HFe-TA degradation and GOx-mediated glucose consumption. Along with this ATP down-regulation, P-gp expression of tumor cells is suppressed remarkably, which in turn promotes the intracellular accumulation and anticancer efficacy of DOX. In addition, the production of OH by Fe ions released from HFe-TA is promoted by the by-products of the oxidation of glucose process by GOx. In consequence, HFe-TA nanocapsules loaded with DOX and GOx enable significant inhibition effect to tumors both in vitro and in vivo due to the synergistic effect of cascade reactions. This study has therefore provided an alternative therapeutic platform for effective tumor inhibition with the potential in overcoming intrinsic MDR.
研究领域:
纳米技术
·
药学
·
癌症研究
·
生物医学工程
✓ 已验证
DOI
高影响因子
BIOMACROMOLECULES
·
2018
·
IF 5.738
Cuiping Jiang,Zitong Qi,Hengbo Jia,Yilei Huang,Yunbo Wang,Wenli Zhang,Zimei Wu,Hu Yang,Jianping Liu
In this work, we report on an ATP-responsive low-molecular-weight polyethylenimine (LMW-PEI)-based supramolecular assembly. It formed via host–guest interaction between PEI (MW = 1.8 kDa)-α-cyclodextrin (α-CD) conjugates and PEI1.8k-phenylboronic acid (PBA) conjugates. The host–guest interaction between PEI1.8k-α-CD and PEI1.8k-PBA was confirmed by the 2D-NOESY chromatogram experiment and competition test. The ATP-responsive property of the supramolecular assembly was evaluated by a series of ATP-triggered degradation and siRNA release studies in terms of fluorescence resonance energy transfer, agarose gel electrophoresis assay, and the time course monitoring of the particle size and morphology. Confocal laser scanning microscopy confirmed the intracellular disassembly of the supramolecular polymer and the release of siRNA. The supramolecular assembly showed high buffering capability and was capable of protecting siRNA from RNase degradation. It had high cytocompatibility according to in vitro cytotoxicity and hemolysis assays. LMW-PEI-based supramolecular assembly facilitated cellular entry of siRNA via energy-dependent endocytosis. Moreover, the assembly/SR-A siRNA polyplexes at N/P ratio of 30 was most effective in knocking down SR-A mRNA and inhibiting uptake of modified LDL. Taken together, this work shows that ATP-responsive LMW-PEI-based supramolecular assembly is a promising gene vector and has potential application in treating atherosclerosis.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2022
·
IF 5.062
Yawei Wang,Hongbing Lin,Xuetao Zhao,Tong Ding,Yuqin Shen
Periodontitis is a chronic inflammatory disease characterized by alveolar bone loss , which affects the integrity of the tissue supporting the teeth. Previous studies have shown that reactive oxygen species (ROS) can promote the secretion of inflammatory factors and cause alveolar bone inflammatory reactions and bone resorption. Therefore, scavenging ROS is important for reducing the expression of inflammatory factors and improving the inflammatory environment of alveolar bone tissue. Superoxide dismutase (SOD) is one of the most effective antioxidant enzymes for eliminating ROS, which can protect cells from ROS toxicity and reduce the level of intracellular oxidative stress and inflammation. However, SOD molecules have shortcomings, such as short half-life and insufficient stability, which limit the application of SOD in inhibiting periodontal bone resorption. The use of carrier zeolitic imidazolate framework-90 (ZIF-90) with ATP-responsiveness and good biocompatibility can protect SOD molecules, improve SOD stability, and achieve intracellular SOD delivery. Therefore, we fixed SOD into ZIF-90 using the co-precipitation method to prepare ATP-responsive [email protected] and designed a study to investigate the ability of ATP-responsive [email protected] to reduce the inflammatory response of lipopolysaccharide (LPS)-stimulated human osteoblast MG-63. In our study, the ATP-responsive assembly efficiently suppressed the levels of ROS and pro-inflammatory cytokines, showing great potential to ameliorate the levels of oxidative stress, reduce inflammation, and increase osteoblast activity. This provides a novel idea for the application of SOD in alveolar bone resorption.
研究领域:
药学
·
生物材料
·
口腔科学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Jingjing Shen,Kai Feng,Jing Yu,Yaxuan Zhao,Ruifang Chen,Hehua Xiong,Yiling Ruan,Zhengtao Xu,Tao Zhang,Xiaolian Sun
Ferroptosis is an iron-dependent form of programmed cell death with the potential to reverse traditional cancer therapy resistance. The combination of ferroptosis with chemotherapy, photodynamic therapy and X-ray therapy has demonstrated remarkably improved therapeutic efficiency. Radiopharmaceutical therapy (RPT) is an emerging approach that achieves precise radiation to diseased tissues via radionuclide delivery. However, insufficient accumulation and retention of therapeutic radiopharmaceuticals in tumor region as well as cancer radioresistance impact treatment efficacy. Here, a nanoassembly of renal clearable ultrasmall iron nanoparticles (USINPs) and 131 I-aPD-L1 is prepared via the affinity of fluorophenylboronic acid modified on the USINPs with 131 I-aPD-L1. The 150 nm USINAs( 131 I-aPD-L1) nanoassembly is stable in blood circulation, effectively targets to the tumor and disassembles in the presence of ATP in the tumor microenvironment. Both in vitro and in vivo experiments prove that USINPs-induced ferroptosis boosted the tumor radiosensitization to 131 I while 131 I-mediated RPT further enhanced ferroptosis. Meanwhile, the immunogenic cell death caused by RPT and ferroptosis combined with PD-L1 immune checkpoint blockade therapy exhibits a strong antitumor immunity. This study provides a novel way to improve the tumor accumulation of ferroptosis inducer and radiopharmaceuticals, insights into the interaction between RPT and ferroptosis and an effective SPECT-guided ferroptosis-enhanced radio-immunotherapy.
研究领域:
纳米技术
·
放射学
·
肿瘤学
·
免疫治疗
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2021
·
IF 4.749
Cuiping Jiang,Yuan Wang,Peiyi Liang,Yao Chen,Ziming Zhuang,Lu Zhang,Yankui Yi,Li Liu,Qiang Liu
Specific delivery of NCEH1 plasmid is a promising approach to boost the cholesterol removal from lipid-laden macrophages for antiatherosclerosis. Polyethylenimine (PEI) is one of the most efficient gene carriers among nonviral vectors. However, the high transfection activity of PEI is always accompanied by profound cytotoxicity. To tackle the paradox between transfection efficiency and safety, we constructed a novel ATP-responsive multifunctional supramolecular polymer by cross-linking functionalized low-molecular-weight PEI via a boronic ester bond for NCEH1 plasmid delivery. The supramolecular polymer could condense NCEH1 plasmids to form stable nanosized polyplexes when the w/w ratios of the polymer and gene were higher than 2. ATP-triggered degradation of the polymer and pDNA release were characterized by a series of studies, including 1H NMR, 31P NMR, XPS, agarose gel electrophoresis, and ethidium bromide exclusion tests. In addition, the changes in particle size and morphology were observed in the presence of ATP. Interestingly, the supramolecular polymer showed broad spectrum antioxidant activities by measuring the elimination rates of different reactive oxygen species. In addition, the supramolecular polymer displayed a high buffering capability and good cytocompatibility as demonstrated by the results of the buffering capacity, a hemolysis assay, and a cytotoxicity test. Importantly, it was revealed that the supramolecular polymer/NCEH1 plasmid polyplex formulated at a w/w ratio of 20 was most effective in enhancing cholesterol removal from lipid-laden macrophages and reducing the accumulation of lipid droplets as evidenced by transfection study, cholesterol efflux assay, and oil red O staining studies. Collectively, the ATP-responsive multifunctional supramolecular polymer holds great potential for safe and efficient gene delivery for antiatherosclerosis.
研究领域:
生物技术
·
药学
·
分子生物学
·
心血管疾病
✓ 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）