ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Jingru Cui,Zhonghui Xue,Zhengxian Zhang,Huanhuan Zhu,Mingsan Miao,Yagang Song,Xiaofang Li,Huahui Zeng,Xiangxiang Wu
Chemodynamic therapy (CDT) is currently constrained by insufficient endogenous H 2 O 2 , enhanced antioxidant defense, weakly acidic conditions in pancreatic cancer. However, the CDT's immunotherapeutic potential hinges on radical-mediated immunogenic cell death (ICD) induction, motivating development of potent self-cascading radical nanogenerators. Herein, this work engineers carrier-free nanoparticles (IAA NPs) through metal-organic self-assembly of Fe 3+ , artesunate (AS) and PD-L1 antibody (αPD-L1), exhibiting high drug loading (AS: 80.62%, Fe 3+ : 4.57%, and αPD-L1: 14.81%), excellent stability and GSH/pH-dependent drug release. IAA NPs achieve GSH-triggered Fe 3+ reduction to Fe 2+ , catalyzing AS decomposition into carbon-centered radicals, with this radicalogenesis being H 2 O 2 /pH-independent while concurrently depleting intratumoral GSH antioxidant. These free radicals effectively induce ICD via apoptosis pathway, eliciting CRT exposure, HMGB1/ATP release, and efficient DC maturation. In Pan02 tumor-bearing mice, IAA NPs efficiently triggers ICD, promoting DC maturation, intratumoral CD4 + /CD8 + T-cell infiltration, and markedly inhibiting tumor growth. Concurrently, αPD-L1 blocks PD-1/PD-L1 pathway and restores T cell recognition, thereby enhancing the antitumor immune response. In addition, the favorable pharmacokinetic profiles, coupled with inherent biocompatibility and biosafety, collectively enhance IAA NPs’ translational potential. Basically, IAA NPs represent a novel strategy to improve combination chemodynamic-immunotherapy through radical-induced ICD and PD-L1 blockade.
研究领域:
纳米医学
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癌症免疫治疗
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化学动力学治疗
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药物递送系统
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生物无机化学
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肿瘤微环境
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免疫学
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International Journal of Pharmaceutics-X
·
2026
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IF 6.4
Xu Luo,Ziqiong Yang,Jianqiu Chen,Mengqi Shen,Kun Wang,Qian Du
Colorectal cancer chemotherapy faces challenges with low intratumoral drug accumulation and off-target toxicity. Micellar liposome complex carriers are a promising anti-cancer platform due to their high encapsulation efficiency, responsive release, and multi-targeting capabilities. This study explores a novel tumor-targeted chemotherapy approach by encapsulating GSH/NQO1-responsive SN38 prodrug micelles into cholesterol-replacement multifunctional liposomes. Timosaponin AIII (TAIII), a steroid saponin with anticancer activity, substitutes cholesterol to stabilize liposomes, benefiting from its steroidal aglycone structure. Additionally, TAIII mimics PEGylation via its glucose moiety, enhancing tumor targeting via the overexpression of glucose transporter 1 (GLUT1) on cancer cells. Molecular docking studies with AutoDock revealed that GLUT1 residues stabilize TAIII in the binding pocket through hydrogen bonding, hydrophobic, and polar interactions, promoting its transmembrane transport. A specific amphiphilic SN38 prodrug, PEG-SS-SN38-QPA (PSSQ), was synthesized and self-assembled into micelles via a solvent injection-dialysis method for GSH/NQO1-responsive controlled drug release in the tumor microenvironment. PSSQ micelles were integrated into the hydrophilic cavity of TAIII-based liposomes (TLP, prepared by the thin-film hydration method) through passive encapsulation to form PSSQ@TLP. In vitro release study exhibiting GSH/NQO1-triggered release under simulated tumor microenvironment. In vitro cytotoxicity evaluation was performed using the MTT assay on HCT116, LOVO, CT26.WT cell lines. Following in vivo evaluations of biodistribution, anti-tumor efficacy, and biosafety in CT26.WT xenograft tumor-bearing mice, PSSQ@TLP demonstrated enhanced intratumoral accumulation, robust tumor suppression, and minimized systemic toxicity, underscoring its promise as a targeted therapeutic strategy for colorectal cancer.
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PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2021
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IF 4.821
Xiaojing Yang,Yingying Wang,Jingjing Xu,Mei-Xia Zhao
In recent years, carbon dots (CDs) have shown potential applications in fluorescence tracing and imaging due to their excellent optical and chemical properties. In this work, a new type of carbon dots (Cy7-CDs) with near-infrared absorption and emission was synthesized from cyanine dyes and polyethylene glycol by hydrothermal reaction. The prepared Cy7-CDs exhibited low toxicity and excellent biocompatibility, which were applied to detect the noble metal ions Au 3+ /Hg 2+ and glutathione via the ‘on–off-on’ mode. In addition, in vivo fluorescence images demonstrated that Cy7-CDs could efficiently accumulate in the tumor. Therefore, Cy7-CDs could act as a multi-functional probe for biological sensing and tumor diagnosis.
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NanoImpact
·
2021
·
IF 5.316
Wanjun Zhang,Jinling Gao,Lin Lu,Tsendmaa Bold,Xin Li,Shuo Wang,Zhishang Chang,Jing Chen,Xiao Kong,Yuxin Zheng,Mingliang Zhang,Jinglong Tang
Glutathione (GSH) and glutathione-S-transferases (GSTs) are two frontlines of cellular defense against both acute and chronic toxicity of xenobiotics-induced oxidative stress. The contribution of GSH and GST enzymes to signaling pathways and the regulation of GSH homeostasis play a central role in the detoxification of numerous environmental toxins and impurities. Iron oxide nanoparticles stemmed from traffic exhaust, steel manufacturing, or welding as a potential environmental pollution can lead to adverse respiratory outcomes and aggravate the risk of chronic health conditions via persistent oxidative stress. In this work, two kinds of acute exposure experiments of iron oxide (Fe 2 O 3 and Fe 3 O 4 ) nanoparticles in cells and in vivo were conducted to evaluate the GSH levels and GST activity. Our current research presented Fe 3 O 4 nanoparticles at lower concentrations (≤100 μg/ml) seem to be more toxic to the human bronchial epithelial cells as their consumption of GSH and decrease of GST activity. The catalysis activity of Fe 3 O 4 nanoparticles per se may contribute to the intracellular GSH consumption along with inhibition of glutathione-S-transferase class mu 1 and P (GSTM1 and GSTP1) active site and expression decrease of GSTM1 and GSTP1. Accordingly, the GSH consumption and decrease in GST activity directed to the further lipid peroxidation regarded as an earlier marker for toxicity evaluation of iron oxide nanoparticles, and relevant intervention may be effective for prevention of respiratory exposure induced damage from iron oxide nanoparticles.
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PubMed
高影响因子
CERAMICS INTERNATIONAL
·
2020
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IF 3.83
Jinyue Zhang,Mingshi Jin,Yong Il Park,Longyi Jin,Bo Quan
Manganese silicate nanoparticles have recently attracted great attention due to the effectiveness of T 1 -weighted magnetic resonance imaging (MRI) contrast agents (CAs) in the mildly acidic and high glutathione (GSH) conditions of the tumor microenvironment. Herein, ultra-small hollow manganese silicate (UHMS) nanoparticles were prepared via a facile, economical, and eco-friendly method based on a hydrothermal process using small silica nanoparticles as both the silicon source and templates. The nanoparticles showed remarkable biocompatibility and dispersion stability after modification with polyethylene glycol (PEG). Owing to their ultra-high longitudinal relaxation rate (r 1 ) at low pH values and high GSH levels, the [email protected] nanoparticles have performed an excellent pH/GSH-responsive T 1 -weighted MRI. Meanwhile, the nanoparticles showed insignificant cytotoxicity in vitro and in vivo. Therefore, the [email protected] nanoparticles show promise as T 1 -MRI CAs in the tumor microenvironment and may be used to assist in clinical cancer diagnosis.
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ANALYST
·
2020
·Vol. 145
·期 8
·2982-2987
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IF 3.978
Jia Li,Yuhui Wang,Shan Sun,A-Man Lv,Kai Jiang,Yike Li,Zhongjun Li,Hengwei Lin
Herein, we report a turn-on fluorimetric nanoprobe for intracellular glutathione (GSH) imaging. The principle of this probe is designed on the basis of the selective reduction between GSH and disulfide bond-based self-crosslinked red emissive carbon dots (abbreviated as SCCDs). The nanoprobe (i.e., SCCDs) was facilely fabricated from thiol-modified carbon dots (CDs) through oxidation in the presence of H2O2, and its fluorescence was greatly reduced due to the effect of aggregation induced quenching (AIQ). However, in the presence of GSH, the SCCDs were separated into many single CDs. As a result, the fluorescence of the nanoprobe was recovered in a GSH concentration-dependent manner, which is the basis for the quantitative analysis of GSH. The nanoprobe shows excellent specificity and a linear range from 0 to 0.15 mM towards GSH with a limit of detection (LOD) of 5.7 μM. Finally, the nanoprobe was demonstrated to have extremely low cytotoxicity, and was successfully applied for monitoring the GSH level in living cells. This work would provide a promising probe for the research of GSH in cytobiology.
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PubMed
高影响因子
Molecular Catalysis
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2020
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IF 3.687
Caixia Cui,Hong Ming,Linjing Li,Mingjie Li,Jian Gao,Tao Han,Yunyun Wang
We report here adopting a glucose template for synthesizing mesoporous silica for enzyme in-situ immobilization. Bifunctional GSH synthetase (GSHF) and polyphosphate kinase (PPK) were selected as model system for synthesizing GSH with ATP regeneration. Results indicated that a pore size that was slightly smaller than that of enzyme was responsible for the high performance of immobilized enzyme inside mesoporous without protein leaking. Then, the cationic dopamine was used for PPK immobilization by self-polymerization. The co-immobilized enzyme activity was much higher than that of the free enzyme. The catalytic efficiency kcat/Km of co-immobilized enzyme was higher than that of the free enzyme (8.5 and 1.5 times higher for GSHF and PPK, respectively). After optimizing the reaction parameters, the co-immobilized enzymes exhibited excellent operational and storage stability, and could be re-used seven times and retained the original activity after 30 days. It is hoped that these findings will pave the way for applying enzyme co-immobilization to biocatalytic system.
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Nanoscale
·
2020
·Vol. 12
·期 32
·16738-16754
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IF 6.895
Weidong Fei,Danfei Chen,Hongxia Tang,Chaoqun Li,Weizeng Zheng,Fengying Chen,Qianqian Song,Yunchun Zhao,Yu Zou,Caihong Zheng
Ferroptosis, a cell death path induced by the generation of reactive oxygen species (ROS), will cause the accumulation of lipid peroxides (PL-PUFA-OOH) and achieve potent tumor-regression. However, glutathione (GSH)-dependent glutathione peroxidase 4 (GPx4) can reduce PL-PUFA-OOH and antagonize the ferroptosis inducing effect of ROS. Herein, folate-PEG modified dihydroartemisinin (DHA) loaded manganese doped mesoporous silica nanoparticles (described as nanomissiles) were constructed for integrating the effect of GSH exhaustion and ROS generation. After endocytosis by tumor cells, intracellular GSH triggered the degradation of nanomissiles, which allowed the simultaneous release of DHA and Fenton catalytic Mn2+ due to the redox reaction between the manganese–oxygen bonds and GSH. The degradation would lead to GSH exhaustion, activation of Mn2+-based magnetic resonance imaging (MRI), and DHA-driven ˙OH generation. The GSH-free environment inhibited the activity of GPx4 and enhanced the accumulation of PL-PUFA-OOH oxidized by ˙OH. Furthermore, the cooperative effects suppressed tumor metastasis by destroying the structure of polyunsaturated fatty acids in the cell membranes and showed potent antitumor activity. This innovative ferroptotic therapy integrating the GSH exhaustion and ROS generation will be a promising strategy for cancer therapy.
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高影响因子
CHEMISTRY OF MATERIALS
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2016
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IF 9.407
Qiuju Li,Min Chen,Daoyong Chen,Limin Wu
Nano drug delivery systems have attracted much research and clinical interest but they remain challenging with respect to developing controllable, nontoxic, biocompatible and biodegradable nanocarriers. Herein, we report the first pH- and glutathione (GSH)-responsive diphenylalanine (FF)-based hybrid spheres using natural alginate dialdehyde (ADA) as the cross-linker to induce self-assembly of FF and an in situ reducer of Au3+ ions into Au nanoparticles (Au NPs). Not only is the synthesis simple and high-yielding, but also these biocompatible hybrid spheres can encapsulate more than 95% of hydrophobic drug (camptothecin, CPT). Moreover, the CPT-loaded carriers are stable under normal physiological environments, and have excellent pH- and GSH-responsive release at pH 5.0 with 10 mM GSH, which is similar to the tumor microenvironment. Also, these nanocarriers can be taken up by cancer cells and have greater cytotoxicity than free drugs. These attributes make nanospheres very promising for drug loading and delivery, and the method may be used for synthesis of other natural nanospheres as delivery systems.
研究领域:
药学
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生物材料科学
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纳米医学
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Inorganic Chemistry Frontiers
·
2023
·Vol. 10
·期 14
·4045-4053
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IF 7
Zhaoguo Hong,Xin You,Jingjing Zhong,Di Yao,He-Dong Bian,Shulin Zhao,Liangliang Zhang,Hong Liang,Fu-Ping Huang
Chemodynamic therapy (CDT), in which highly toxic hydroxyl radicals (˙OH) could be triggered by a Fenton or Fenton-like reaction to kill cancer cells, has emerged recently. Compared to traditional CDT nanomaterials, herein, an atomically-precise biotinylated Cu(I/II) complex [CuICuIICl2(VBio)]·CH3OH (VBio = deprotonated O-vanillin biotinylhydrazone), denoted VBio-CuICuII, was rationally designed and synthesized successfully. This targeted Fenton-like agent, VBio-CuICuII, is constructed from a hydroxyl radical-producible CuI ion, a CuII center as a GSH depletor for an augmented CDT effect, and a biotin moiety as a cancer-targeting unit. Owing to the obvious cell selectivity discrepancy of biotin towards normal and cancerous cells, VBio-CuICuII was able to preferentially accumulate in tumor cells. Meanwhile, the CuI metal center could be used as a Fenton-like agent to generate ˙OH. Furthermore, the CuII in VBio-CuICuII was available for successive ˙OH production via a CuI/CuII-circulation strategy under a GSH-rich tumor site, thereby improving catalytic efficiency. More importantly, in vivo results further demonstrate that VBio-CuICuII could significantly inhibit tumor growth without obvious damage toward major organs. Therefore, this multiple-identity Fenton-like agent could provide an appreciable reference value for the design of atomically precise CDT agents.
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Qiuxing Liu,Xin Ding,Xiaoyu Xu,Hualu Lai,Zishan Zeng,Ting Shan,Tao Zhang,Meixu Chen,Yanjuan Huang,Zeqian Huang,Xiuling Dai,Meng Xia,Shengmiao Cui
Tumor cells with innate oxidative stress are more susceptible to exogenous ROS-mediated oxidative damage than normal cells. However, the generated ROS could be scavenged by the overexpressed GSH in cancer cells, thus causing greatly restricted efficiency of ROS-mediated antitumor therapy. Herein, using cinnamaldehyde (CA) as a ROS generator while β-phenethyl isothiocyanate (PEITC) as a GSH scavenger, we designed a tumor-targeted oxidative stress nanoamplifier to elevate intracellular ROS level and synchronously suppress antioxidant systems, for thorough redox imbalance and effective tumor cells killing. First, an amphiphilic acid-sensitive cinnamaldehyde-modified hyaluronic acid conjugates (HA-CA) were synthesized, which could self-assemble into nano-assembly in aqueous media via strong hydrophobic interaction and π-π stacking. Then, aromatic PEITC was appropriately encapsulated into HA-CA nano-assembly to obtain HA-CA/PEITC nanoparticles. Through enhanced permeability retention (EPR) effect and specific CD44 receptor-mediated endocytosis, HA-CA/PEITC nanoparticles could accumulate in tumor tissues and successfully release CA and PEITC under acidic lysosomal environment. Both in vitro and in vivo results showed that the nanoparticles could efficiently boost oxidative stress of tumor cells via generating ROS and depleting GSH, and finally achieve superior antitumor efficacy. This nanoamplifier with good biosafety provides a potential strategy to augment ROS generation and suppress GSH for enhanced oxidation therapy.
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MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Baocheng Tian,Hong Xu,Haiyan Wang,Keke Li,Shuna Zheng,Senhao Hu,Yongjun Wang,Qingzhi Lv
Photothermal therapy, combined with chemotherapy, holds promising prospects for the therapeutic outcome of malignant tumors. However, the synergistic therapeutic effect suffers from low coloading capacity and inefficient synchronous tumor-targeting delivery of chemodrug and photothermal photosensitizers. Herein, we designed a versatile carrier-free nanoplatform to seek improvement for chemo-photothermal therapy. An NIR photosensitizer IR-808 was used for noninvasive cancer imaging, diagnosis, and imaging-guided photothermal therapy. A reduction-sensitive paclitaxel prodrug (PTX-SS-PEG2k) was rationally synthesized by covalently linking paclitaxel with polyethylene glycol 2000 via a disulfide bond. Then, the carrier-free nanoassemblies were constructed with an inner core of IR-808 and an amphiphilic paclitaxel prodrug shell. PTX-SS-PEG2k served as a stabilizer and chemodrug and could facilitate the self-assembly of IR-808 nanoparticles with high coloading efficiency and reduction-sensitive drug release. The versatile nanoplatform exhibited multiple advantages, including high drug payload, reduction-sensitive drug release, tumor-targeting drug delivery, and potent synergistic antitumor effect. We provide a versatile theranostic nanoplatform, which improves the effectiveness of synergetic chemo-photothermal therapy and reduces the off-target toxicity.
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高影响因子
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