INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2015
·
IF 3.65
Jing Li,Tingjie Yin,Lei Wang,Lifang Yin,Jianping Zhou,Meirong Huo
Tumor-targeted drug delivery and microenvironment-responsive drug release are attractive strategies in cancer treatment. Our previous study demonstrated that redox-sensitive micelles based on hyaluronic acid-deoxycholic acid (HA-ss-DOCA) conjugates exhibited excellent drug-loading capacities (34.1%) for paclitaxel (PTX) and rapid drug release in response to reducing agent, glutathione . In the present study, the physicochemical and biological properties of PTX-loaded HA-ss-DOCA (PTX-HA-ss-DOCA) micelles were investigated further. The micelles have an average size of about 120 nm and a zeta potential of about −36 mV. Transmission electron microscopy and wide-angle X-ray diffraction analysis demonstrated redox-sensitive degradation of micelles in the presence of glutathione. Moreover, the encapsulated payload was effectively released from HA-ss-DOCA micelles into cytoplasm and then rapidly transported into nuclei. In vitro cytotoxicity and cell apoptosis assay further revealed that HA significantly improved the tumor-specific drug delivery of HA-ss-DOCA micelles via receptor-mediated endocytosis, while efficient intracellular drug release and transportation lead to marked inhibition of tumor cell growth, as compared to Taxol ® and insensitive micelles. More importantly, PTX-HA-ss-DOCA micelles demonstrated superior in vivo antitumor activity compared with Taxol ® and insensitive control, and decreased systemic toxicity. Herein we present data which provide valuable insight into the design and development of tumor-specific drug delivery systems .
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高影响因子
Advanced Science
·
2025
·
IF 14.1
Yanan Wang,Xutao Ma,Xinyuan Wang,Liru Liu,Xue Zhang,Qiuyue Wang,Yingfei Zhu,Huanhua Xu,Liangmin Yu,Zhiyu He
The scarcity of effective neuroprotective agents and the presence of blood-brain barrier (BBB)-mediated extremely inefficient intracerebral drug delivery are predominant obstacles to the treatment of cerebral ischemic stroke (CIS). Herein, ROS-responsive borneol-based amphiphilic polymeric NPs are constructed by using traditional Chinese medicine borneol as functional blocks that served as surface brain-targeting ligand, inner hydrophobic core for efficient drug loading of membrane-permeable calcium chelator BAPTA-AM, and neuroprotective structural component. In MCAO mice, the nanoformulation (polymer: 3.2 mg·kg −1 , BAPTA-AM: 400 µg·kg −1 ) reversibly opened the BBB and achieved high brain biodistribution up to 12.7%ID/g of the total administered dose after 3 h post single injection, effectively restoring intracellular Ca 2+ and redox homeostasis, improving cerebral histopathology, and inhibiting mitochondrial PI3K/Akt/Bcl-2/Bax/Cyto-C/Caspase-3,9 apoptosis pathway for rescuing dying neurons (reduced apoptosis cell from 59.5% to 7.9%). It also remodeled the inflammatory microenvironment in cerebral ischemic penumbra by inhibiting astrocyte over-activation, reprogramming microglia polarization toward an anti-inflammatory phenotype, and blocking NF-κB/TNF- α /IL-6 signaling pathways. These interventions eventually reduced the cerebral infarction area by 96.3%, significantly improved neurological function, and restored blood flow reperfusion from 66.2% to ≈100%, all while facilitating BBB repair and avoiding brain edema. This provides a potentially effective multiple-stage sequential treatment strategy for clinical CIS.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 14
·6654
·
IF 4.9
Zhenrong Liu,Zhe Zong,Xiaoxin Li,Shaoping Sun
In this paper, a multifunctional polymer BT-PGA-TPE-HNPE was designed and synthesized by modifying γ-polyglutamic acid (γ-PGA) with biotin, the tetraphenylethylene derivative O-TPE-HNPE and an acid-sensitive imine bond. The polymer was used to fabricate paclitaxel (PTX)-loaded micelles. As expected, the BT-PGA-TPE-HNPE micelles demonstrated strong AIE characteristics, fluorescing yellow under normal conditions and blue in acidic settings. Moreover, the drug was specifically released under acidic conditions. In vitro and in vivo tumor suppression experiments showed that the micelles had enhanced antitumor activity with minimal systemic toxicity. The BT-PGA-TPE-HNPE micelles had wide application prospects in the fields of chemotherapy and bioimaging.
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FOOD CHEMISTRY
·
2025
·
IF 9.8
Xue-Chen Pei,Fa-Wen Yin,Meng-Ling Jin,Xin-Miao Wang,Hui-Lin Liu,Liang Song,Bei-Wei Zhu,Da-Yong Zhou
Water-soluble copper (CuSO 4 ), oil-soluble copper and different amount of water were added to demetallized and dehydrated Antarctic krill oil (AKO) for accelerated storage. The results showed that water-soluble copper (100 μmol/kg oil) could not significantly promote the oxidation of dehydrated AKO. While water-soluble copper (100 μmol/kg oil) exhibited stronger prooxidative property than oil-soluble copper (100 μmol/kg oil) in AKOs adding water. Meantime, with prolonged storage time of AKO adding water, the size of reverse micelle increased, the electronegativity and surface tension of the oil-water interface decreased, and adding water-soluble copper ions aggravated the above changes. Therefore, it was speculated that Cu 2+ is adsorbed to the oil-water interface by the action of electric charge to promote the oxidation of phospholipids containing unsaturated fatty acids (UFAs) and free UFAs present at the interface by initiating the free radical chain reaction, thereby accelerating the oxidation of AKO.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 23
·期 20
·12624
·
IF 6.208
Shanming Zhang,Fen Zheng,Kaige Liu,Shengke Liu,Tonghu Xiao,Yabin Zhu,Long Xu
Mitochondrial DNA and nuclear DNA are essential genetic material which play an important role in maintaining normal metabolism, survival, and proliferation of cells. Constructing a mitochondria-targeting stimuli-responsive nano-drug delivery system releasing chemotherapeutic agents in a stepwise response manner and destroying mitochondrial DNA and nuclear DNA simultaneously is an effective way to improve the anti-tumor effect of chemotherapeutic agents. In this study, a new mitochondria-targeting pH/ROS dual-responsive block copolymer TPP-PEG2k-b-(BS-AA)n(P1), untargeted pH/ROS dual-responsive copolymer mPEG2k-b-(BS-AA)n(P2), pH single-responsive copolymer (mPEG2k-b-(AH-AA)n(P3), ROS single-responsive copolymer mPEG2k-b-(SA-TG)n(P4), and non-responsive copolymer mPEG-b-PCL (P5) were constructed. pH/ROS-responsive properties were characterized by proton nuclear magnetic resonance (1H NMR) and dynamic light scattering (DLS). Anticancer chemotherapeutic agent gemcitabine (GEM) or fluorescent substance Nile Red (NR) were loaded in the polymer micelles. Results of the mitochondrial colocalization experiment indicate that (5-carboxypentyl)(triphenyl)phosphonium bromide (TPP)-functionalized P1 micelles could be efficiently targeted and located in mitochondria. Results of the cellular uptake experiment showed that pH/ROS dual-responsive GEM-loaded P1 and P2 micelles have faster internalized and entry nucleus rates than single-responsive or non-responsive GEM-loaded micelles. The in vitro release experiment suggests pH/ROS dual-responsive GEM/P1 and GEM/P2 micelles have higher cumulative release than single-responsive GEM/P3 and GEM/P4 micelles. The in vitro cytotoxic experiment shows that the mitochondria-targeted dual-responsive GEM/P1 micelles had the lowest IC50 values, and the cytotoxic effect of dual-responsive GEM/P2 micelles was superior to the single-responsive and non-responsive drug-loaded micelles.Keywords:mitochondria-targeted;pH/ROS dual-responsive;acetal;thioether;TPP
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2012
·
IF 3.456
Qian Guo,Ping Luo,Yu Luo,Fang Du,Wei Lu,Shiyuan Liu,Jin Huang,Jiahui Yu
Biodegradable micelles with sheddable poly(ethylene glycol) shells were fabricated based on poly(ethylene glycol)- block -poly(γ-benzyl l -glutamate) (mPEG-SS-PBLG) diblock copolymer and applied as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38) in order to enhance its solubility and stability in aqueous media. The diblock polymer was designed to have the hydrophilic PEG moiety and hydrophobic PBLG moiety linked by biodegradable disulfide bond, so in reducing environment the PEG shells can be detached. The polymer was able to form the micelles of nano-scale in aqueous media, suggesting their passive targeting potential to tumor tissue. Water-insoluble antitumor drug, SN-38, was easily encapsulated into mPEG-SS-PBLG nanomicelles by lyophilization method. When setting theoretical drug loading content at 10 wt%, the drug encapsulation efficiency (EE) was assayed as 73.5%. Owing to the disulfide bond in mPEG-SS-PBLG, intense release of SN-38 occurred in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition, however, micelles showed gradual release of SN-38 in the absence of DTT. Also, the mPEG-SS-PBLG micelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition. Compared with free SN-38, SN-38-loaded nanomicelles showed essentially decreased cytotoxicity against L929 cell line in 24 h, bare mPEG-SS-PBLG nanomicelles showed almost non-toxicity.
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Applied Materials Today
·
2020
·
IF 8.352
Liping Yuan,Meng Pan,Minyi Lei,Xingli Zhou,Danrong Hu,Qingya Liu,Yu Chen,Wei Li,Zhiyong Qian
Transdermal drug delivery is an attractive and potentially more effective method of localized and systemic treatment with minimal side effects and greater safety than current techniques. However, a limitation of drug delivery through the skin is the presence of the stratum corneum, which inhibits the development of clinical applications. Furthermore, in order to achieve better therapeutic outcomes, a number of traditional topically-applied preparations have high drug concentrations which can lead to skin irritation and formation of lesions. The use of safer and milder hydrocortisone (HC) cream for the treatment of moderate to severe atopic dermatitis (AD) is not considered due to its low potency and poor absorption through the skin, even at a dose of 1%. Therefore, in the present study, a composite of HC-loaded micelles and carbomer hydrogel was designed to enhance transdermal HC transport to improve topical therapy of AD. Franz diffusion cell experiments indicated that this composite significantly increased the skin permeation rate and cumulative quantity of HC transferred, which were greater than a 9-fold and 50-fold increase relative to HC cream, respectively. In addition, the composite system was demonstrated to rapidly and effectively ameliorate inflammatory symptoms on an AD-like mouse model and greatly reduce skin irritation and adverse systemic effects compared to HC cream. As described above, the novel HC formulation was a feasible strategy to provide safe and effective treatment in AD therapy.
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Nano-Micro Letters
·
2020
·Vol. 12
·期 1
·1-19
·
IF 12.264
Cheng Hao,Zhang Huaqing,Xu Gujun,Peng Jin,Wang Zhen,Sun Bo,Aouameur Djamila,Fan Zhechen,Jiang Wenxin,Zhou Jianping,Ding Yang
AbstractSection
Highlights
A combined assembly strategy from hydrophobicity-driving and reversible borate bridges is proposed for high drug-loading efficiency and superior stability.
Intestinal environment-triggered drug delivery system represents an effective treatment for local infection due to the site-specific targeting and shuttling of drugs.
The reduced dosage brought by the drug-loading micelles could solve the problem of drug residue in breeding industry.
AbstractSection
Abstract
Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs. Herein, chitosan conjugates (SPCS) installed with sialic acid (SA) and phenylboronic acid (PBA) were synthesized, of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA. The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges. The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract. After reaching the lesions, the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release, while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside. The drug-micelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation. The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable, safe and flexible anti-infectious drug delivery systems.
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International Journal of Nanomedicine
·
2023
·
IF 8
Chen Xu,Ri-jin Song,Pei Lu,Jian-chun Chen,Yong-qiang Zhou,Gang Shen,Min-jun Jiang,Wei Zhang
Aim To significantly promote cancer cell uptake and to achieve combination therapy and on-demand drug release, a pH-triggered charge-switchable and redox-responsive drug-release nanovehicle was developed in this study.Materials and methods The nanocarrier was constructed by conjugating 3,3′-dithiodipropionic acid-modified doxorubicin (DTPA-DOX) and 2,3-dimethylmaleic anhydride (DMA) to the side amino groups of poly(ethylene glycol)-b-poly(L-lysine) (PEG-b-PLL) and by encapsulating triptolide (TRI) into the hydrophobic core. The surface charge of the obtained nanocarriers (DA-ss-DT) can change from negative to positive in response to tumor extracellular acidity pH, and the nanocarriers capably release two drugs in response to intracellular high glutathione (GSH) environment.Results Compared to the control group, the in vitro cellular uptake of DA-ss-DT by human prostate cancer PC-3 cells was significantly promoted in slightly acidic conditions, and the drug could be rapidly released in the high concentration of GSH conditions. The in vitro and in vivo antitumor experiments exhibited that the DA-ss-DT nanoparticles have a great antitumor effect in comparison to the control group.Conclusion These findings demonstrated that the DA-ss-DT nanoparticles supply a useful strategy for promoting cellular uptake and synergetic anticancer therapy.
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Polymer Chemistry
·
2014
·Vol. 6
·期 11
·1952-1960
·
IF 5.368
Hanmei Li,Hao Jiang,Mengnan Zhao,Yao Fu,Xun Sun
An amphiphilic cationic graft polymer polyethylenimine-cystamine-poly(ε-caprolactone) (PSSP) with intracellular redox potential-responsive cleavable ability was synthesized for the first time by coupling poly(ε-caprolactone) (PCL) to polyethylenimine (PEI) via a bio-cleavable disulfide linkage. PSSP based micelles, which can degrade in the intracellular reducing environment, were developed as smart non-viral gene vectors for enhanced miR-34a delivery. The PSSP/miR-34a complexes showed effective and stable miRNA condensation with a narrow particle size of around 120 nm. The gel retardation assay showed that PSSP micelles could protect miRNA from RNase and achieve intracellular release of miRNA in the reducing environment. Compared with PEI-25k, PSSP revealed comparable transfection efficiencies in the B16F10 cell with less cytotoxicity. The B16F10 cell treated with PSSP/miR-34a complexes showed a significantly higher cell apoptosis than the PEI-25k/miR-34a complexes. These encouraging results indicated that PSSP may possess promising potential as a smart non-viral gene vector with low cytotoxicity, intracellular redox potential to trigger miRNA release and high transfection efficiency.
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ACS Biomaterials Science & Engineering
·
2017
·
IF 3.234
Yushu Huang,Ya Gao,Tiandong Chen,Yanyun Xu,Wei Lu,Jiahui Yu,Yi Xiao,Shiyuan Liu
The aim of this research is to develop a novel type of camptothecin (CPT) prodrug micelles bearing boronate ester bonds as a smart nanosystem with enhanced cellular uptake and controlled drug release based on diblock copolymer abbreviated as PEG-BC-PGlu-ss-CPT. Particularly, boronate ester bond was introduced to achieve acid-triggered de-PEGylation and succeeding boronic acid-mediated enhanced cellular uptake. Besides, CPT was conjugated to the prodrug monomer through a disulfide bond to realize reduction-responsive drug release. The resultant copolymer PEG-BC-PGlu-ss-CPT could self-assemble into spherical nanomicelles in water. The degradation half-life time of PEG-BC-PGlu-ss-CPT copolymer decreased sharply from 96.27 h to only 5.7 h with pH value decreasing from 7.4 to 5.0, indicating the acid-degradable potential, which corresponded to size change monitoring. The cumulative CPT release from prodrug micelles increased significantly from 8.5 ± 1.73 to 82.9 ± 2.29% with an increase of dithiothreitol (DTT) concentration from 20 μM to 10 mM at pH 7.4, illustrating the reduction-responsive drug release property of prodrug micelles. The half maximal inhibitory concentration (IC50) value of prodrug micelles against HepG2 cells decreased from 1.06 to 0.68 μg/mL with the decrement of pH value from 7.4 to 6.0, proving that the utilization of boronate ester bonds was beneficial for enhancing antiproliferative activity. Interestingly, prodrug micelles exhibited enhanced cellular uptake ability against HepG2 cells compared to that of HL7702 cells, further confirming boronic acid-mediated enhanced endocytosis. In brief, this novel type of intelligent prodrug micelles possessed great potential as a smart nanosystem for antitumor drug delivery.
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Advanced Healthcare Materials
·
2021
·Vol. 10
·期 24
·2100356
·
IF 9.933
Zhen Jiang,Boyang Sun,Yueqi Wang,Heqi Gao,He Ren,Hao Zhang,Tong Lu,Xiangkui Ren,Wei Wei,Xiaoli Wang,Lei Zhang,Jiao Li,Dan Ding,Jonathan F. Lovell,Yumiao Zhang
Aggregation-induced emission luminogens (AIEgens) hold promise for biomedical imaging and new approaches facilitating their aggregation state are desirable for fluorescence enhancement. Herein, a series of surfactant-stripped AIEgen micelles (SSAMs) with improved fluorescence are developed by a low-temperature surfactant-stripping method to encapsulate AIEgens in temperature-sensitive Pluronic block copolymer. After stripping excessive surfactant, SSAMs exhibit altered optical properties and significantly higher fluorescence quantum yield. Using this method, a library of highly concentrated fluorescent nanoparticles are generated with tunable absorption and emission wavelengths, permitting imaging of deep tissues at different wavelengths. SSAMs remain physiologically stable and can pass safely through gastrointestinal tract (GI) without degradation in the harsh conditions, allowing for fluorescence and photoacoustic imaging of intestine with high resolution. d -amino acids (DAA), a natural metabolite for bacteria, can be chemically conjugated on the surface of SSAMs, enabling non-invasive monitoring of the microbial behavior of ex vivo fluorescently labeled gut microbiota in the GI tract.
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