Nanoscale Research Letters
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2022
·Vol. 17
·期 1
·1-16
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IF 5.418
Wang Chonggao,Cheng Xiaolan,Peng Hao,Zhang Yewei
Although being the first-line treatment of advanced hepatocellular carcinoma (HCC), sorafenib (SOR) outcome is limited due to drug resistance and low tumor accumulation. Herein, with MnO 2 as photothermal agent and chlorine6 (Ce6) as photosensitizer, a tumor-targeting and NIR-triggered multifunctional nanoplatform loading sorafenib (MnO 2 -SOR-Ce6@PDA-PEG-FA, MSCPF) was constructed. Owing to oxygen generator MnO 2 , MSCPF could generate excessive ROS, thus can alleviate tumor hypoxia and improve sorafenib accumulation in cancer cells. Besides, ROS production further strengthens Ce6-mediated PDT and PDA-mediated PTT. By exploiting these features, MSCPF exhibited excellent antitumor effects on HCC in the in vitro and in vivo studies, compared to solo sorafenib or PDT/PTT treatment. Further mechanism experiments suggested that MSCPF could inhibit P-gp expression and induce ferroptosis via deactivation of GPX4 and SLC7A11, which ultimately enhanced the antitumor efficacy of SOR. In summary, our work highlights a promising NIR-triggered and ROS-boosted nanoplatform for enhanced chemo/PDT/PTT synergistic therapy of SOR in HCC treatment.
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BIOMATERIALS
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2022
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IF 15.304
Yan Gao,Zilin Song,Li Jia,Yi Tang,Chengcheng Wang,Xiuli Zhao,Haiyang Hu,Dawei Chen,Mingxi Qiao
Despite the important role of reactive oxygen species (ROS) in battling cancer, ROS production with current approaches has been severely limited by the deficiency of oxy-substrates in tumor microenvironment . Herein, an atorvastatin (Ato)-catalytic self-amplified approach was utilized for sustainable ROS production and enhancing anti-tumor efficacy of PD-L1 silencing. A C 18 -pArg 8 -ss-pHis 10 lipopeptide based self-assembled nanoplexes was developed to co-encapsulate AMP-activated protein kinase (AMPK) activator of Ato and PD-L1 siRNA. Efficient delivery of payloads was achieved because of the acidic pH triggered the protonation of pHis 10 , disulfide-bond exposure for cleavage and subsequent cytosolic translocation. Ato was found to activate AMPK, boosting the highly restrained mitochondrial fatty acid oxidation (FAO) in cancer cells for ROS production. The ROS derived from FAO further activated AMPK, creating a positive-feedback mechanism of sustainable ROS production. The self-amplified ROS production from cellular mitochondrial FAO was maintained by the sufficient intracellular fatty acid substrates arising from the dysregulated lipid metabolism and Ato inhibited triglyceride synthesis in cancer cells. The excessive ROS level was found to successfully induce immunogenic cell death effect, boosting the anti-tumor efficacy of PD-L1 silencing. Overall, the Ato catalyzed self-amplified ROS production has been demonstrated as a promising alternative for cancer therapy.
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Applied Materials Today
·
2022
·
IF 8.663
Jiaxin Zhang,Mingxi Yang,Xiaoduo Tang,Shuang Li,Junhu Zhang,Laijin Lu,Quan Wang,Bai Yang
Radiation enteritis is an unavoidable complication of radiotherapy for pelvic tumors that seriously affects the prognosis of cancer patients. The fundamental mechanism inducing cell death and tissue injury is the generation of excessive reactive oxygen species (ROS) by ionizing radiation. In the present study, we developed novel S-doped red fluorescent carbonized polymer dots (S-rCPDs) with high biocompatibility and efficient ROS-scavenging capability to act as an intestinal protective agent against radiation damage. The S-rCPDs significantly eliminates cellular ROS and alleviates DNA damage under X-ray radiation. To achieve drug accumulation within the distal intestine, S-rCPDs loaded pH-controlled release polymer microspheres ( [email protected] ) is produced via microfluidic technology. In vivo experimental results show that oral administration of [email protected] effectively suppresses the secretion of pro-inflammatory cytokines and alleviates acute radiation intestinal injury, with a better protective effect than amifostine, which is hereto the only clinically approved radioprotector. Moreover, the as-prepared [email protected] could stabilize the balance of intestinal flora and continuously downregulate the expression of transforming growth factor β1 (TGF-β1), eventually inhibiting the progression of chronic intestinal fibrosis. This study provides a novel strategy for whole-course treatment of radiation enteritis using CPDs-based materials, which could inspire the development of other radioprotective nano-drugs.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Chenlan Xu,Shuting Chen,Cuiping Chen,Yangcan Ming,Jiahao Du,Jinyi Mu,Fang Luo,Da Huang,Na Wang,Zhenyu Lin,Zuquan Weng
Co-delivery of anti-inflammatory drugs and reactive oxygen species (ROS) scavengers by stimuli-responsive oral nanoparticles is deemed to be a favorable strategy for inflammatory bowel disease (IBD) therapy. In this study, using micelles formed by CUR conjugated hydroxyethyl starch (HES) as vehicles, dexamethasone (DEX)-loaded HES-CUR nanoparticles (DHC NPs) with desirable size, negative surface charge, good stability in the harsh gastric environment, and excellent ROS scavenging activity are developed as a colon-targeted oral formulation for treating IBD. Due to the degradation of HES in response to α-amylase overexpressed in the inflamed colon, the DHC NPs release drugs in an α-amylase-responsive manner. Meanwhile, the DHC NPs can be effectively internalized by macrophages and show excellent cytocompatibility with macrophages since they are composed of food-derived compounds. Importantly, in vivo studies reveal that the DHC NPs are capable of targeting the inflamed colon induced by dextran sulfate sodium (DSS), and the targeted and combination therapy enhances the efficacy of free DEX and significantly relieves the impairment caused by DSS-induced ulcerative colitis. Incorporating the merits of targeted drug delivery and combined therapy with an anti-inflammatory drug and ROS scavenger, the DHC NPs are promising for developing novel oral formulations for IBD therapy.
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Materials Today Bio
·
2022
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IF 10.761
Chen Tan,Heng Fan,Jiahui Ding,Chaoqun Han,Yang Guan,Feng Zhu,Hui Wu,Yujin Liu,Wei Zhang,Xiaohua Hou,Songwei Tan,Qing Tang
Oxidative stress, caused by excessive production of reactive oxygen species (ROS), plays a crucial role in the occurrence and development of ulcerative colitis (UC). We developed ROS-responsive nanoparticles (NPs) as an efficacious nanomedicine against UC with oral administration. The NPs were fabricated with a d -α-tocopherol polyethylene glycol succinate-b-poly(β-thioester) copolymer (TPGS-PBTE) for ROS cleavage via the colitis-targeted delivery of luteolin (LUT), a natural flavonoid with good anti-inflammation and radical-scavenging activity. Owing to the thioether bond in the polymer main chain, the TPGS-PBTE NPs exhibited an ROS-responsive size change and drug release, which benefited the ROS-scavenging and selective accumulation of LUT in the inflamed colon. In a dextran sulfate sodium-induced acute colitis murine model, [email protected] NPs alleviated body weight loss, colon length shortening, and damage to the colonic tissues due to the suppression of ROS and proinflammatory cytokines (e.g., IL-17A, IL-6, interferon-γ, tumor necrosis factor-α), as well as upregulation of glutathione and anti-inflammatory factors (e.g., IL-10, IL-4). More importantly, [email protected] NPs regulated the inflammatory microenvironment by modulating the T helper (Th)1/Th2 and Th17/regulatory T cell (Treg) balance (i.e., increased numbers of Tregs and Th2 cells and decreased numbers of Th1 and Th17 cells), thus resolving inflammation and accelerating the healing of the intestinal mucosa. Additionally, the [email protected] NPs formulation enabled the reduction of the effective dose of LUT and showed excellent biosafety in the mouse model, demonstrating its potential as a targeted UC therapeutic oral preparation.
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JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-18
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IF 9.429
Ma Jun,Zhou Yi,Li Jiaying,Song Zhiyong,Han Heyou
Background The study of symbiotic nitrogen fixation between (SNF) legumes and rhizobia has always been a hot frontier in scientific research. Nanotechnology provides a new strategy for biological nitrogen fixation research. However, how to construct abiotic nano-structure-biological system, using the special properties of nanomaterials, to realize the self-enhancement of biological nitrogen fixation capacity is important.Results In order to construct a more efficient SNF system, in this study, we applied manganese ferrite nanoparticles (MF-NPs) with sustainable diatomic catalysis to produce reactive oxygen species (ROS), thus regulating the nodulation pathway and increasing the number of nodules in soybean (Glycine max), eventually enhancing symbiotic nitrogen fixation. Symbiosis cultivation of MF-NPs and soybean plants resulted in 50.85% and 61.4% increase in nodule weight and number, respectively, thus inducing a 151.36% nitrogen fixation efficiency increase, finally leading to a 25.70% biomass accumulation increase despite no substantial effect on the nitrogenase activity per unit. Transcriptome sequencing analysis showed that of 36 differentially expressed genes (DEGs), 31 DEGs related to soybean nodulation were upregulated in late rhizobium inoculation stage (12 d), indicating that the increase of nodules was derived from nodule-related genes (Nod-R) continuous inductions by MF-NPs.Conclusion sOur results indicated that the nodule number could be effectively increased by extending the nodulation period without threatening the vegetative growth of plants or triggering the autoregulation of nodulation (AON) pathway. This study provides an effective strategy for induction of super-conventional nodulation.Graphical Abstract
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Advanced Science
·
2023
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IF 15.1
Jiayin Yu,Zhihao Guo,Jiachang Yan,Changxin Bu,Chang Peng,Cuie Li,Rui Mao,Jian Zhang,Zhi Wang,Shi Chen,Meicun Yao,Zhiyong Xie,Chuan Yang,Yi Yan Yang,Peiyan Yuan,Xin Ding
Helicobacter pylori ( H. pylori ) has infected more than half of the world's population, and is the major cause of gastric cancer. The efficacy of standard antibiotic-based triple therapy is declining due to drug resistance development. Herein, a pH-responsive reactive oxygen species (ROS) nanogenerator (Fe-HMME@DHA@MPN) composed of acid-responsive metal polyphenol network (MPN) shell and mesoporous metal-organic nanostructure core [Fe-HMME (hematoporphyrin monomethyl ether, sonosensitizer)] loaded with dihydroartemisinin (DHA) is reported. These nanoparticles generate more ROS singlet oxygen than sonosensitizer HMME under ultrasonication, and this sonodynamic process is fueled by oxygen generated through Fenton/Fenton-like reactions of the degraded product in gastric acid Fe (II) and hydrogen peroxide (H 2 O 2 ) in the infection microenvironment. The encapsulated DHA, as a hydroperoxide source, is found to enhance the peroxidase-like activity of the Fe-HMME@DHA@MPN to generate ROS hydroxyl radical, beneficial for the microenvironment without sufficient H 2 O 2 . In vitro experiments demonstrate that the ROS nanogenerators are capable of killing multidrug-resistant H. pylori and removing biofilm, and ROS nanogenerators show high therapeutic efficacy in a H. pylori infection mouse model. Unlike the triple therapy, the nanogenerators display negligible side effects toward the normal gut microbiota. Taken together, these self-enhanced ROS nanogenerators have a great potential for treatment of H. pylori infection.
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JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 15
Pang Wenyang,Cao Yin,Du Shuang,Liang Zuowen,Wang Hongliang,Liu Lingyun
Background Tire wear particles (TWPs) are a major source of micro- and nanoplastics. However, reports on nanoscale tire wear particles, especially regarding their potential hazards to the male reproductive system, remain scarce. Results Here, we examined whether nanoscale tire wear particles impair spermatogenesis and blood-testis barrier integrity through ROS-linked ferroptotic injury. Using a 70-day oral exposure model in pubertal male mice and complementary GC-2 and TM4 cell models, we found that high-dose particle exposure reduced epididymal sperm density, increased sperm abnormalities, disrupted seminiferous epithelial organization, and increased BTB permeability. TWPs shifted metabolomic profiles toward lipid and iron dysregulation, suppressed SLC7A11/GPX4, increased ACSL4 and labile Fe²⁺, and depleted junctional proteins. Ferrostatin-1 reduced lipid peroxidation, iron accumulation, cell death, and junctional protein loss, indicating a functional contribution of ferroptosis. Mechanistically, TWPs first induced total and mitochondrial reactive oxygen species and mitochondrial depolarization, which were restrained by N-acetylcysteine. Downstream, autophagic ferritin degradation amplified ferroptotic injury, as chloroquine or NCOA4 knockdown preserved ferritin, reduced malondialdehyde accumulation, restored GPX4/SLC7A11, and improved viability. NCOA4 depletion did not substantially blunt ROS induction, placing ferritinophagy after redox imbalance. Conclusions Together, these data define a ROS-initiated, NCOA4-dependent ferritinophagy-ferroptosis axis that connects nanoscale TWPs to BTB failure and impaired spermatogenic homeostasis. This work provides a mechanistic basis for future assessment of reproductive health risks associated with TWPs exposure. Graphical abstract
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CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Weiyong Tao,Xiaodan Wu,Jiaqi Li,Feige Wu,Chen Chen,Ting Jiang,Cunjing Xu,Shangtong Jiang,Jianglin Wang,Bo Xiao,Yingying Du,Shengmin Zhang
The anti-cancer effect of selenite (SeO 3 2− ) is limited by its short half-life and narrow therapeutic window. Peroxynitrite (ONOO − ), the most active reactive nitrogen species (RNS) derived from nitric oxide (NO) reacting with superoxide anion (O 2 •− ), is still not fully exploited in the combination therapy against cancers. Herein, an injectable hydrogel is developed to trigger intracellular reactive oxygen species (ROS)/RNS bursts and disrupt nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis via an innovative SeO 3 2− -based strategy. Calcium selenite/ L -Arginine ( L -Arg) nanospheres (SL NPs) are synthesized as the donor of NO and SeO 3 2− . The injectable Alg@SLGA sol composed of SL NPs, glucose oxidase (GOx), 6-aminonicotinamide (6-AN, an inhibitor of the pentose phosphate pathway (PPP)), and sodium alginate (Alg) can convert to gel in a physiological environment. Peritumoral injection of Alg@SLGA hydrogel is performed for safe and targeted treatment. The loaded GOx catalyzes glucose oxidation to produce acidic H 2 O 2 , initiating the release of NO and SeO 3 2− from Alg@SLGA. SeO 3 2− reacts with intracellular GSH and H 2 O 2 to generate •OH and O 2 •− , which further interacts with NO to form ONOO − . The SeO 3 2− and 6-AN synergistically trigger intracellular NADPH exhaustion by promoting cystine metabolism-mediated NADPH consumption and inhibiting NADPH generation, respectively. Moreover, Alg@SLGA effectively induces immunogenic cell death (ICD) of tumor cells, further provoking systemic antitumor immune responses. As a consequence, the injectable Alg@SLGA hydrogel achieves enhanced ROS/RNS-mediated combination therapy by synergistically disrupting NADPH homeostasis and improving antitumor immunity.
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EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
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2020
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IF 5.573
Jianqiang Qian,Zhongyuan Xu,Chi Meng,Ji Liu,Pei-Ling Hsu,Yangyang Li,Weizhong Zhu,Yumin Yang,Susan L. Morris-Natschke,Kuo-Hsiung Lee,Yanan Zhang,Yong Ling
Oxidative therapy, a strategy that specifically increases reactive oxygen species (ROS) levels in tumor cells by disrupting the redox homeostasis has gained increasing interest. The antitumor effects of the natural product piperlongumine (PL) appear to result from its ability to increase intracellular ROS levels via inhibition of antioxidative thioredoxin reductase (TrxR). Twenty-seven benzylidenecyclohexenone-based PL analogues ( 2a-v and 15a-e ) were designed, synthesized and evaluated for their pharmacological properties . Most of the compounds exhibited potent antiproliferative activities against five human cancer cell lines, especially against breast tumor cells. One of the most promising analogueues 2c showed 12-fold higher inhibitory activity against the thioredoxin reductase (TrxR) than PL and surpressed the expression of TrxR1 protein in breast cancer cells and inhibited TrxR enzymatic activity . In addition, 2c increased ROS levels and resulted in marked apoptosis by regulating apoptosis-related proteins expressed in the breast cancer cells. Compound 2c also triggered the formation of autophagosomes and autolysosomes by promoting the expression of LC3-II and Beclin-1 and diminishing the expression of LC3-I and p62 proteins. Finally, 2c displayed low acute toxicity and good inhibitory potency to tumors in mice. Overall, 2c is a promising anti-breast cancer candidate warranting further investigation.
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Advanced Healthcare Materials
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2023
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IF 10
Yupeng Guan,Hanqi Lei,Chengyuan Xing,Binyuan Yan,Bingbiao Lin,Xiangwei Yang,Hai Huang,Yang Kang,Jun Pang
Chemotherapy remains the most essential treatment for prostate cancer, but multidrug resistance (MDR) contributes to chemotherapy failure and tumor-related deaths. The overexpression of P-glycoprotein (P-gp) is one of the main mechanisms behind MDR. Here, we report a multimodal nanoplatform with a reactive oxygen species (ROS) cascade for gas therapy/ferroptosis/chemotherapy in reversing MDR. The nanoplatform disassembles when responding to intracellular ROS and exerts three main functions: First, NO-targeted delivery could reverse MDR by downregulating P-gp expression and inhibiting mitochondrial function. Second, ferrocene-induced ferroptosis breaks the redox balance in the tumor intracellular microenvironment and synergistically acts against the tumor. Third, the release of paclitaxel is precisely controlled in situ in the tumor for chemotherapy that avoids damage to normal tissues. Excitingly, this multimodal nanoplatform is a promising weapon for reversing MDR and may provide a pioneering paradigm for synergetic cancer therapy. This article is protected by copyright. All rights reserved
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KAOHSIUNG JOURNAL OF MEDICAL SCIENCES
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2023
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IF 3.3
Peng-Cheng Zhong,Zhi-Wen Liu,Qi-Chang Xing,Jia Chen,Rui-Pei Yang
Non-small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer cases. Neferine is used as a traditional Chinese medicine with many pharmacological effects, including antitumor properties; however, it has not been reported whether neferine plays an anticancer role by causing pyroptosis in NSCLC cells. We used two typical lung cancer cell lines, A549 and H1299, and 42 lung cancer tissue samples to investigate the regulatory effects of neferine on TGF-β and MST1. We also treated lung cancer cells with different concentrations of neferine to study its effects on lung cancer cell survival, migration, invasion, and epithelial–mesenchymal transition (EMT) as well as on pyroptosis. Lentivirus-mediated gain-of-function studies of TGF-β and MST1 were applied to validate the roles of TGF-β and MST1 in lung cancer. Next, we used murine transplanted tumor models to evaluate the effect of neferine treatment on the metastatic capacity of lung cancer tissues. With increasing neferine concentration, the viability, migration, invasion, and EMT capacity of A549 and H1299 cells decreased, whereas pyroptosis increased. Neferine repressed TGF-β expression to modulate the induction of reactive oxygen species (ROS) by MST1. Overexpression of TGF-β in either in vitro or mouse-transplanted A549 cells restored the inhibitory effect of neferine on tumor development. Overexpression of MST1 clearly enhanced pyroptosis. Neferine contributed to pyroptosis by regulating MST1 expression through downregulation of TGF-β to induce ROS formation. Therefore, our study shows that neferine can serve as an adjuvant therapy for NSCLC patients.
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