Advanced Healthcare Materials
·
2020
·Vol. 9
·期 20
·2000432
·
IF 7.367
Genhua Liu,Liucan Wang,Junjie Liu,Lu Lu,Dong Mo,Ke Li,Xin Yang,Rui Zeng,Jixi Zhang,Peng Liu,Kaiyong Cai
Inhibiting the function of P-glycoprotein (P-gp) transporter, which causes drug efflux through adenosine triphosphate (ATP)-dependent manner, has become an effective strategy to conquer multidrug resistance (MDR) of cancer cells. However, there remains challenges for effective co-delivery, sequential release of P-gp modulator and chemotherapeutic agent. In this work, a novel type of core–shell nanoparticle is reported. It can independently encapsulate a high amount (about 683 µg mg −1 ) of chemotherapeutic agent doxorubicin (DOX) in the mesoporous polydopamine (MPDA) core and glucose oxidase (GOx) in the zeolite imidazolate frameworks-8 (ZIF-8) shell, namely MPDA@ZIF-8/DOX+GOx. The fast release of GOx triggered by acid-sensitive degradation of the ZIF-8 shell consumes glucose to starve cancer cells for ATP deprivation and effective suppress ATP-dependent drug efflux in advance, and then effectively facilitates the accumulation of DOX in MCF-7/ADR cancer cells. Experiments in vitro and in vivo demonstrate that the fabricated nanosystem can dramatically improve anticancer effects for MDR through sequential release property and exhibit excellent biocompatibility. Overall, this work reveals new insights in the use of GOx for MDR treatment.
研究领域:
纳米技术
·
药学科学
·
癌症研究
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Zhanwei Zhou,Chenzi Li,Minghua Zhang,Qingyan Zhang,Chenggen Qian,David Oupicky,Minjie Sun
Hydrophobic modification on polycations were commonly used to improve the stability and transfection efficiency of polyplexes. However, the improved stability often means undesired release of the encapsulated siRNA, limiting the application of cationic micelles for siRNA delivery. The current strategy of preparing bioresponsive micelles based on the cleavage of sensitive linkages between polycation and hydrophobic part was far from sufficient, owing to the siRNA binding of the separated polycations from micelles leading to the incomplete release of siRNA. In this study, we propose a new strategy by the combination of micelles disassembly and separated polycations charge reversal. FPBA (3-fluoro-4-carboxyphenylboronic acid) grafted PEI 1.8 k (polyethylenimine) as the polycations of PEI-FPBA and dopamine (with diol-containing moiety) conjugated with cholesterol as the hydrophobic part (Chol-Dopa). The PFCDM micelles was assembled by PEI-FPBA and Chol-Dopa, based on the FPBA-Dopa conjugation. The prepared PFCDM showed strong siRNA loading ability and superior stability in the presence of PBS or serum. Besides, the PFCDM exhibited excellent ATP sensibility. The intracellular ATP could effectively trigger the disassembly of micelles and charge reversal of PEI-FPBA, resulting in the burst release of siRNA in the cytosol. With the property of extracellular stability and intracellular instability, PFCDM displayed good performance on in vitro and in vivo luciferase silencing on 4T1 cells. It should also be noted that the assembly of low molecular weight PEI was relatively safe to cells compared with 25 k PEI. To sum up, the ATP-fueled assembly and charge reversible micelles gave examples for polyplexes to achieve better stability and on demand cargo release at the same time and shows potential to be used for in vitro and in vivo siRNA transfection.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2023
·Vol. 190
·期 11
·1-9
·
IF 5.7
Yao Yuying,Wang Yeru,Zhu Jingru,Guo Zhiqiang,Li Zongqiang,Li Qianru,Liu Su,Wang Yu,Yu Jinghua,Huang Jiadong
A DNA triangular prism nanomachine (TPN)–based logic device for intracellular AND-gated imaging of adenosine triphosphate (ATP) has been constructed. By using i-motif sequences and ATP-binding aptamers as logic control units, the TPN logic device is qualified to respond to the acidic environment and ATP in cancer cell lysosomes. Once internalized into the lysosome, the specific acidic microenvironment in lysosome causes the i-motif sequence to fold into a tetramer, resulting in compression of DNA tri-prism. Subsequently, the split ATP aptamer located at the tip of the collapsed triangular prism binds stably to ATP, which results in the fluorescent dyes (Cy3 and Cy5) modified at the ends of the split aptamer being in close proximity to each other, allowing Förster Resonance Energy Transfer (FRET) to occur. The FRET signals are excited at a wavelength of 543 nm and can be collected within the emission range of 646–730 nm. This enables the precise imaging of ATP within a cell. We also dynamically operate AND logic gates in living cells by modulating intracellular pH and ATP levels with the help of external drugs. Owing to the AND logic unit on TPN it can simultaneously recognize two targets and give corresponding intelligent logic judgment via imaging signal output. The accuracy of molecular diagnosis of cancer can be improved thus eliminating the false positive signal of single target-based detection. Hence, this space-controlled TPN-based logical sensing platform greatly avoids sensitivity to extracellular targets during the cell entry process, providing a useful tool for high-precision imaging of the cancer cell’s endogenous target ATP.
研究领域:
分子生物学
·
纳米医学
·
生物成像
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
·
2023
·
IF 8.8
Jian Sun,Huayi Qu,Waseem Ali,Yan Chen,Tao Wang,Yonggang Ma,Yan Yuan,Jianhong Gu,Jianchun Bian,Zongping Liu,Hui Zou
Microplastics (MPs) and cadmium (Cd) are important environmental pollutants, that damage the liver. However, the effect and mechanism of combined Cd and MPs exposure on liver fibrosis are still largely unknown. In this study investigated, Cd + MPs exposure increased superoxide anion production and promoted extracellular ATP release compared with exposure to Cd or MPs individually. Cd + MPs increased inflammatory cell infiltration , activated the P2X7-NLRP3 signaling pathway, and promoted inflammatory factor release. Cd + MPs aggravated Cd- or MPs-induced liver fibrosis and induced liver inflammation. In AML12/HSC-T6 cell in vitro poisoning model, exposure of AML12 cells to Cd + MPs increased the opening of connexin hemichannels and promoted extracellular ATP release. Treatment of HSC-T6 cells with the supernatant of AML12 cells exposed to Cd + MPs significantly promoted HSC-T6 cell activation. Treatment of HSC-T6 cells with different concentrations of ATP produced similar results. TAT-Gap19TFA, an inhibitor of connexin hemichannels, significantly inhibited the ATP release and activation of Cd + MPs-treated HSC-T6 cells. Finally, the expression of the ATP receptor P2X7 was silenced in HSC-T6 cells, which significantly inhibited their activation. In conclusion, exposure to Cd + MPs promoted liver fibrosis through the ATP-P2X7 pathway and synergistically affected liver inflammation and fibrosis.
研究领域:
环境科学
·
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2014
·
IF 6.451
Siqi Zhang,Amin Bao,Ting Sun,Erkang Wang,Jiahai Wang
By virtue of a biomimetic nanopore and single-walled carbon nanotubes, a new sensor for adenosine triphosphate (ATP) detection is designed. As compared to the routine approach, the present scenario does not entail the surface modification of nanopore with analyte-specific probes. The underlying mechanism relies on a symmetric nanopore sequentially modified with polyethyleneimine (PEI) and Zr 4+ that can quantitate the concentration of ATP-bound aptamer, while other free aptamers are removed by single-walled carbon nanotubes (SWNTs). The detection limit of the nanopore sensor is 27.46 nM, and the linear range is from 50 nM to 400 nM. The biosensor with an excellent selectivity against guanosine triphosphate (GTP), uridine triphosphate (UTP), and cytosine triphosphate (CTP) can be applied in the real samples such as Hela cell .
研究领域:
纳米技术
·
生物传感
·
分析化学
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2021
·
IF 4.539
Chenxi Yu,Wenyu Zhu,Zhaozhan He,Jin Xu,Fengyan Fang,Ziang Gao,Wenli Ding,Yixiang Wang,Jing Wang,Junqiao Wang,Ao Huang,Aohua Cheng,Yanhui Wei,Shiyun Ai
Poly(lactic-co-glycolic acid) (PLGA) based microparticles have been widely applied in drug delivery system, but pristine PLGA particles suffers from low efficiency in release and non-targeted effect for drug delivery system. Inspired by cancer cells environment, we have fabricated an ATP-triggered delivery system based on porous PLGA microspheres covering drug-loaded ZIF-90. The system contains controlled doxorubicin releasing because ZIF-90 nanocrystals are easily collapsed under exposing to high-concentration ATP environment. In addition, [email protected] microparticles also perform low toxicity and 2.37 % hemolysis, and improved fluorescence intensity of doxorubicin by loading riboflavin sodium phosphate benefited from their partial Förster resonance energy transfer. This novel ATP-triggered drug delivery system based on porous PLGA particles could be widely utilized to design effective drug release biomaterials for gastric and lung cancer.
研究领域:
药剂学
·
生物材料
·
癌症研究
·
药物传递系统
✓ 已验证
产品关联
DOI
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2017
·Vol. 101
·期 13
·5325-5332
·
IF 3.42
Cao Hao,Nie Kaili,Li Chengcheng,Xu Haijun,Wang Fang,Tan Tianwei,Liu Luo
Adenosine-5′-triphosphate (ATP) is the energy equivalent of the living system. Polyphosphate (polyP) is the ancient energy storage equivalent of organisms. Polyphosphate kinases (PPKs) catalyze the polyP formation or ATP formation, to store energy or to regenerate ATP, respectively. However, most PPKs are active only in the presence of long polyPs, which are more difficult and more expensive to generate than the short polyPs. We investigated the PPK preference towards polyPs by site-directed mutagenesis and computational simulation, to understand the mechanism and further design enzymes for effective ATP regeneration using short polyPs for in vitro cascade reactions, which are highly desired for research and applications. The results suggest that the short polyPs inhibit PPK by blocking the ADP-binding pocket. Structural comparison between PPK ( Corynebacterium glutamicum ) and PPK ( Sinorhizobium meliloti ) indicates that three amino acid residues, i.e., lysine, glutamate, and threonine, are involved in the activity towards short polyP by fixing the adenosine group of ADP in between the subunits of the dimer, while the terminal phosphate group of ADP still offers an active site, which presents a binding pocket for ADP. A proposed triple mutant PPK (SMc02148-KET) demonstrates significant activity towards short polyP to form ATP from ADP. The obtained high glutathione titer (38.79 mM) and glucose-6-phosphate titer (87.35 mM) in cascade reactions with ATP regeneration using the triple mutant PPK (SMc02148-KET) reveal that the tailored PPK establishes the effective ATP regeneration system for ATP-dependent reactions.
研究领域:
生物化学
·
酶工程
·
合成生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Jingyi Yang,Jiahao Qu,Xuanming Teng,Weiping Zhu,Yufang Xu,Yangyang Yang,Xuhong Qian
Most solid tumors are clinically treated using surgical resection, and the presence of residual tumor tissues at the surgical margins often determines tumor survival and recurrence. Herein, a hydrogel (Apt-HEX/Cp-BHQ1 Gel, termed AHB Gel) is developed for fluorescence-guided surgical resection. AHB Gel is constructed by tethering a polyacrylamide hydrogel and ATP-responsive aptamers together. It exhibits strong fluorescence under high ATP concentrations corresponding to the TME (100–500 µ m ) but shows little fluorescence at low ATP concentrations (10–100 n m ) such as those in normal tissues. AHB Gel can rapidly (within 3 min) emit fluorescence after exposure to ATP, and the fluorescence signal only occurs at sites exposed to high ATP, resulting in a clear boundary between the ATP-high and ATP-low regions. In vivo, AHB Gel exhibits specific tumor-targeting capacity with no fluorescence response in normal tissue, providing clear tumor boundaries. In addition, AHB Gel has good storage stability, which is conducive to its future clinical application. In summary, AHB Gel is a novel tumor microenvironment-targeted DNA-hybrid hydrogel for ATP-based fluorescence imaging. It can enable the precise imaging of tumor tissues, showing promising application in fluorescence-guided surgeries in the future.
研究领域:
生物医学工程
·
癌症研究
·
材料科学
·
外科肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-17
·
IF 10.2
Liu Kaiyuan,Zhang Li,Lu Hengli,Wen Yingfei,Bi Bo,Wang Guocheng,Jiang Yingying,Zeng Leli,Zhao Jing
Background Mild-temperature photothermal therapy (mild PTT) is a safe and promising tumor therapeutic modality by alleviating the damage of healthy tissues around the tumor due to high temperature. However, its therapeutic efficiency is easily restricted by heat shock proteins (HSPs). Thus, exploitation of innovative approaches of inhibiting HSPs to enhance mild PTT efficiency is crucial for the clinical application of PTT.Results Herein, an innovative strategy is reported: pyroptosis-boosted mild PTT based on a Mn-gallate nanoformulation. The nanoformulation was constructed via the coordination of gallic acid (GA) and Mn2+. It shows an acid-activated degradation and releases the Mn2+ and GA for up-regulation of reactive oxygen species (ROS), mitochondrial dysfunction and pyroptosis, which can result in cellular ATP deprivation via both the inhibiton of ATP generation and incresed ATP efflux. The reduction of ATP and accumulation of ROS provide a powerful approach for inhibiting the expression of HSPs, which enables the nanoformulation-mediated mild PTT.Conclusion sOur in-vitro and in-vivo results demonstrate that this strategy of pyroptosis-assited PTT can achieve efficient mild PTT efficiency for osteosarcoma therapy.Graphical Abstract
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Yixuan Xu,Huiping Dang,Changchang Teng,Dalong Yin,Lifeng Yan
Rapid propagation of tumor cells requires plenty of energy, which is adenosine triphosphate (ATP) dependent. ATP inhibition in tumors not only results in the starvation of tumor cells but also down-regulation of the level of heat shock proteins (HSPs), which usually increase during traditional photothermal therapy (PTT), especially when the temperature is up 50 °C. 2-deoxy-D-glucose (2DG) is an anti-glycolytic reagent and can be used as an efficient agent for ATP inhibition in tumors. Compared with typical PTT, low-temperature mild photothermal therapy (MPTT) is receiving more and more attention because it avoids the high temperatures causing damage to the normal tissue, and the increase of HSPs which decrease PTT. Here, multifunctional polypeptide nanoparticles pDG@Ahx conjugating both a NIR probe Ahx-BDP and 2DG into the side chain of the amphiphilic polypeptide have been prepared. In vitro and in vivo studies reveal that the as-prepared nanoparticles achieve a synergistic effect of starvation/MPTT/PDT (photodynamic therapy), and it provides a new strategy to NIR-I/II fluorescence imaging-guided starvation/MPTT/PDT synergy therapy for tumors.
研究领域:
生物医学工程
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Xianfeng Wang,Xiaolong Chen,Chengxiang Chu,Yuanyi Deng,Mei Yang,Zhong Ji,Faliang Xu,Danqun Huo,Yang Luo,Changjun Hou
High-performance detection of adenosine triphosphate (ATP) is of great importance due to its irreplaceable roles in various physiological processes. In this work, a four-stage signal amplification was established for ATP detection based on an allosteric probe-conjugated strand displacement amplification (SDA) integrated with CRISPR/Cpf1 system (ASD-Cpf1). An allosteric probe (AH) with a hairpin structure was designed to reduce background interference from self-extension and non-specific amplification during the SDA reaction. ATP bound with the aptamer segment at 5′-terminal of AH probe and subsequently opened the AH probe to activate the SDA reaction. The amplification products were recognized by CRISPR/Cpf1 system and triggered the ssDNase activity of Cpf1, resulting in robust cleavage of surrounding DNA FQ-reporter (fluorophore-quencher labeled short single-stranded DNA sequence). With the four-step amplification, ATP was measured with high sensitivity and low background interference. Under the optimal conditions, a linear relationship was obtained between the fluorescence response and ATP concentrations ranging from 2 pM to 10 μM with a limit of detection (LOD) as low as 1.8 pM. Successful detection of ATP in diluted human serum samples further indicated that ASD-Cpf1 system provided a potential platform for detection of small molecules.
研究领域:
分析化学
·
分子生物学
·
生物技术
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Li Li Li,Wen Yi Lv,Yao Wang,Yuan Fang Li,Chun Mei Li,Cheng Zhi Huang
DNA logic nanodevices have prospects in molecular recognitions but still face challenges in achieving DNA computation-controlled regulation in specific compartments of living cells. By incorporating the i-motif sequence and ATP aptamers into a Y-shaped DNA (Y-DNA) structure, and applying gold nanoparticles (AuNPs) as the transporting carrier, herein we present a new type of DNA logic nanodevices to monitor the ATP levels in lysosomes of living cells. Triple energy transfers including dual fluorescent resonance energy transfers (FRETs) and a nanometal surface energy transfer (NSET) occurred in the DNA logic nanodevices. It was identified that the proposed nanodevices perform an AND logic operation to output FRET signals only when an endogenous proton and ATP simultaneously exist in the cellular microenvironment. Owing to the use of the i-motif sequence, the nanodevices have lysosome-recognizing capacity without causing alkalization of the acidic organelle, making DNA computation-controlled regulation at the level of cellular organelles achievable. These DNA logic nanodevices show high application prospects in lysosome-related cellular function and disease treatment.
研究领域:
分子生物学
·
纳米技术
·
细胞生物学
·
生物医学工程
✓ 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）