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Advanced Materials Interfaces · 2023 · IF 5.4

Preparation of ROS-Responsive Exosome Coating of Nitinol Material for Making the Neurointerventional Stent

Lin Duan,Yanyan He,Haigang Wu,Tianxiao Li,Jia Liang,Rufeng Jia,Dehua Guo,Taoyuan Lu,Chi Ma,Wenbo Liu,Yingkun He

Nitinol (NiTi) alloy is an ideal material for preparing neurointerventional stents due to its excellent mechanical properties and biocompatibility. However, NiTi stents without surface-specific functionalization cause a high rate of stent thrombosis and in-stent restenosis after implantation. In ischemic stroke, exosomes have a role in regulating nervous system development, regeneration, vascular remodeling, and neuroinflammation. In this work, the effect of exosome coating on the biocompatibility of NiTi alloy is evaluated. NiTi alloy is successively immersed in relevant solution (sodium alginate, 3-aminophenylboronic acid, distearoylphosphatidylethanolamine, and exosomes) to form ROS-responsive exosome coated surfaces. In vitro experiments (platelets, endothelial cells, smooth muscle cells, and macrophages) and in vivo subcutaneous implantation experiments are performed to test coatings for biocompatibility. The results show that the modified NiTi alloy surface has high hydrophilicity, which has the functions of inhibiting platelet aggregation, promoting endothelialization, inhibiting smooth muscle cell migration, anti-inflammatory, and good tissue biocompatibility. This study develops exosome neurointerventional stent coating as a bioactive drug via reactive oxygen species accumulation in lesions, thus targeting drug release, inhibiting intimal hyperplasia, and reducing inflammation and thrombosis.

CAS / MDL: 6066-82-6 9005-38-3
研究领域: 材料科学 · 生物医学工程 · 神经科学 · 生物材料 · 组织工程
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Biomaterials Science · 2023 ·Vol. 11 ·期 14 ·4930-4937 · IF 6.6

ROS conversion promotes the bactericidal efficiency of Eosin Y based photodynamic therapy

Birong Fan,Wan Peng,Yu Zhang,Pingsheng Liu,Jian Shen

Photodynamic therapy (PDT) is becoming an efficient antibacterial strategy without drug-resistance. Here, we report a promising reactive oxygen species (ROS) conversion strategy to increase the antibacterial efficiency of an Eosin Y (EOS)-based PDT system. Based on visible-light illumination, EOS generates a high concentration of singlet oxygen (1O2) in the solution. With the introduction of HEPES in the EOS system, it can almost completely convert 1O2 to hydrogen peroxide (H2O2). The orders-of-magnitude increases in the half-lives of the ROS (H2O2vs.1O2) present in the solution can enable more persistent oxidation ability. Thus, it is able to increase the bactericidal efficiency (against S. aureus) from 37.9% to 99.9%, promote the inactivation efficiency of methicillin-resistant S. aureus (MRSA) from 26.9% to 99.4%, and enhance the eradication rate of MRSA biofilm from 69% to 90%. Further in vivo investigation showed that the increased oxidation ability of the EOS/HEPES PDT system can enable quicker healing and maturing (even better than that for vancomycin administration) of MRSA-infected skin wounds on rats. This strategy may find many creative applications for the efficient eradication of bacteria and other pathogenic microorganisms.

CAS / MDL: 17372-87-1 15086-94-9
研究领域: 药理学 · 微生物学 · 生物医学工程 · 传染病学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Applied Materials Today · 2021 · IF 10.041

Porous selenium nanozymes targeted scavenging ROS synchronize therapy local inflammation and sepsis injury

Xu Chen,Xufeng Zhu,Youcong Gong,Guanglong Yuan,Jieqiong Cen,Qiaoshan Lie,Yida Hou,Gang Ye,Shengming Liu,Jie Liu

Excessive reactive oxygen species (ROS) is the main factor leading to high mortality in local inflammation and sepsis. Therefore, developing efficient ROS scavenger in pro-inflammatory immune cells is an urgent strategy for therapy local inflammatory and sepsis injury. Herein, we constructed a novel mesoporous selenium-hyaluronic acid nanoenzyme therapeutic system (MSe-HA NPs) for therapy local inflammatory and sepsis injury by targeting eliminate ROS in inflammatory macrophage. In detail manners, the high specific surface area of mesoporous selenium nanoenzyme exhibited ultra-high activity like glutathione peroxidase (GPx), which catalytic speed of H 2 O 2 scavenging was increasing to 2.02 times compare with solid Se NPs. Moreover, the broad spectrum of ROS eliminating capacity further promoted ability of MSe NPs in eliminating various ROS. More interestingly, we found that choose HA as the modification not only endowed the MSe NPs targeting to inflammatory macrophage, but the ROS degradable property of HA could enhance the MSe NPs to eliminating ROS. In vivo , MSe-HA NPs after injection showed that simultaneously cured the local inflammation and sepsis induced with LPS by quickly eliminating excessive ROS. Especially in sepsis mouse models, the survival rate and the organic dysfunction significantly improved after treated with MSe-HA NPs. Thus, this novel mesoporous nanozyme provides an effective strategy for the design of nanomedicine and the treatment of inflammation-related diseases.

CAS / MDL: 50-81-7 9004-61-9
研究领域: 纳米技术 · 药学 · 免疫学 · 炎症研究 · 败血症治疗
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Bioactive Materials · 2024 · IF 18

ROS-responsive and triple-synergistic mitochondria-targeted polymer micelles for efficient induction of ICD in tumor therapeutics

Xiaoxiao Hu,Mo Zhang,Cuilu Quan,Saisai Ren,Wei Chen,Jing Wang

Immunogenic cell death (ICD) represents a modality of apoptosis distinguished by the emanation of an array of damage-related molecular signals. This mechanism introduces a novel concept in the field of contemporary tumor immunotherapy. The inception of reactive oxygen species (ROS) within tumor cells stands as the essential prerequisite and foundation for ICD induction. The formulation of highly efficacious photodynamic therapy (PDT) nanomedicines for the successful induction of ICD is an area of significant scientific inquiry. In this work, we devised a ROS-responsive and triple-synergistic mitochondria-targeted polymer micelle (CAT/CPT-TPP/PEG-Ce6, CTC) that operates with multistage amplification of ROS to achieve the potent induction of ICD. Utilizing an “all-in-one” strategy, we direct both the PDT and chemotherapeutic units to the mitochondria. Concurrently, a multistage cyclical amplification that caused by triple synergy strategy stimulates continuous, stable, and adequate ROS generation (domino effect) within the mitochondria of cells. Conclusively, influenced by ROS, tumor cell-induced ICD is effectively activated, remodeling immunogenicity, and enhancing the therapeutic impact of PDT when synergized with chemotherapy. Empirical evidence from in vitro study substantiates that CTC micelles can efficiently provoke ICD, catalyzing CRT translocation, the liberation of HMGB1 and ATP. Furthermore, animal trials corroborate that polymer micelles, following tail vein injection, can induce ICD, accumulate effectively within tumor tissues, and markedly inhibit tumor growth subsequent to laser irradiation. Finally, transcriptome analysis was carried out to evaluate the changes in tumor genome induced by CTC micelles. This work demonstrates a novel strategy to improve combination immunotherapy using nanotechnology.

研究领域: 癌症治疗 · 纳米技术 · 免疫疗法 · 药学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2023 · IF 9.7

Stimuli-responsive nanoparticles delivered by a nasal-brain pathway alleviate depression-like behavior through extensively scavenging ROS

Lin Liu,Min Liu,Jingya Xiu,Bowen Zhang,Haiyang Hu,Mingxi Qiao,Dawei Chen,Jiulong Zhang,Xiuli Zhao

Depression is one of the most common mental diseases, which seriously affects patients’ physical and mental health. Emerging evidence has indicated that oxidative stress (OS) is a major cause of neurodegeneration involved in the pathogenesis of depression. Consequently, targeted reactive oxygen species (ROS) elimination is regarded as a promising strategy for efficient depression therapy. In addition, insufficient brain drug delivery is the main obstacle to depression therapy owing to the presence of the blood-brain barrier (BBB). To achieve the goals of bypassing the BBB and promoting antioxidant therapy for depression, a broad-spectrum ROS scavenging NPs was rationally designed through a nasal-brain pathway developed for combined ROS scavenging and brain drug delivery. A hexa-arginine (R6) modified ROS-responsive dextran (DEX) derivate was synthesized for antidepressant olanzapine (Olz) and H 2 donor amino borane (AB) loading to prepare Olz/RDPA nanoparticles (NPs). Subsequently, the NPs were dispersed into a thermoresponsive hydrogel system based on poloxamer. In vitro and in vivo results demonstrated that Olz/RDPA in situ thermoresponsive hydrogel system could effectively deliver NPs to the brain via the nasal-brain pathway and alleviate depression-like behaviors through combined ROS depletion and inhibition of 5-HT dysfunction of the oxidative stress-induced. The proposed ROS-scavenging nanotherapeutic would open a new window for depression treatment. Statement of Significance ROS is an innovative therapeutic target involving the pathology of depression whereas targeted delivery of ROS scavenging has not been achieved yet. In the current study, ROS-responsive nanoparticles (Olz/RDPA NPs) were prepared and dispersed in a thermosensitive hydrogel for delivery through the nasal-brain pathway for the treatment of depression. Sufficient ROS depletion and improvement of delivery capacity by the nasal-brain pathway effectively could reverse oxidative stress and alleviate depressive-like behavior. Collectively, these nanoparticles may represent a promising strategy for the treatment of depression.

CAS / MDL: 9004-53-9
研究领域: 药学 · 神经科学 · 纳米技术 · 药物递送系统
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CARBOHYDRATE POLYMERS · 2019 · IF 6.044

Novel dual ROS-sensitive and CD44 receptor targeting nanomicelles based on oligomeric hyaluronic acid for the efficient therapy of atherosclerosis

Xiaoya Hou,Hua Lin,Xiudi Zhou,Ziting Cheng,Yi Li,Xue Liu,Feng Zhao,Yanping Zhu,Peng Zhang,Daquan Chen

Although the clinical usage of drugs administration was raising, the application of nanoparticles encapsulating the hydrophobic drugs with plummy efficiency was very scarce for atherosclerosis (AS) treatment. In this work, a novel dual ROS-sensitive and CD44 receptors targeting amphiphilic carrier material, oligomeric hyaluronic acid-2′-[propane-2,2-diyllbls (thio)] diacetic acl-hydroxymethylferrocene (oHA-TKL-Fc), named HASF, was synthesized and characterized by 1 H-NMR spectra. Then, we combined curcumin (Cur) with HASF into nano-micelles ( [email protected] micelles) by self-assembling method. The resulting [email protected] micelles had the average size of 150.8 nm and zeta potential of -35.04 mV to maintain the will-defined spheroidal structure and stability. Importantly, the [email protected] micelles had ultrahigh entrapment efficiency (about 51.41 %). Moreover, in vitro release study, Cur release from [email protected] micelles was effective in the reactive oxygen species (ROS) condition, and the release rate was interrelated with the concentration of hydrogen peroxide (H 2 O 2 ). Further, fluorescence imaging showed that the [email protected] micelles could more selective access to Raw 264.7 cells than free Cur via oHA-receptor mediated endocytosis. The MTT assay attested the safety of amphiphilic carrier material HASF. Additionally, the results of in vivo Oil red O lipid staining studies showed that the lesion area of the aorta was reduced to 47.3±3.4 % with [email protected] micelles, compared with the lesion area of Cur group (63.2±2.7 %), [email protected] micelles had the more remarkable effect in reducing lesion area (*P < 0.05). Consequently, the novel dual ROS-sensitive and CD44 receptors targeting drug delivery system would become a promising strategy for atherosclerosis.

CAS / MDL: 7722-84-1
研究领域: 药学 · 纳米技术 · 心血管疾病
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JOURNAL OF HAZARDOUS MATERIALS · 2024 · IF 12.2

Cd exposure confers β-cypermethrin tolerance in Lymantria dispar by activating the ROS/CnCC signaling pathway-mediated P450 detoxification

Mingtao Tan,Hong Jiang,Rusong Chai,Miao Fan,Zengting Niu,Guotong Sun,Shanchun Yan,Dun Jiang

Heavy metal pollutants are important abiotic environmental factors affecting pest habitats. In this study, Cd pre-exposure significantly increased the tolerance of Lymantria dispar larvae to β-cypermethrin, but did not significantly alter their tolerance to λ-cyhalothrin and bifenthrin. The activation of P450 by Cd exposure is the key mechanism that induces insecticide cross-tolerance in L. dispar larvae. Both before and after β-cypermethrin treatment, Cd exposure significantly increased the expression of CYP6AB224 and CYP6AB226 in L. dispar larvae. Silencing CYP6AB224 and CYP6AB226 reduced the tolerance of Cd-treated L. dispar larvae to β-cypermethrin. Transgenic CYP6AB224 and CYP6AB226 genes significantly increased the tolerance of Drosophila and Sf 9 cells to β-cypermethrin, and the recombinant proteins of both genes could significantly metabolise β-cypermethrin. Cd exposure significantly increased the expression of CnCC and Maf . CnCC was found to be a key transcription factor regulating CYP6AB224 - and CYP6AB226 -activated insecticide cross-tolerance in Cd-treated larvae. Decreasing reactive oxygen species (ROS) levels in the Cd-treated larvae or increasing ROS levels in the untreated larvae reduced or enhanced the expression of CnCC , CYP6AB224 and CYP6AB226 and β-cypermethrin tolerance in L. dispar larvae, respectively. Collectively, Cd exposure confers β-cypermethrin tolerance in L. dispar larvae through the ROS/ CnCC signalling pathway-mediated P450 detoxification. Environmental Implication Heavy metals have been reported to produce cross-tolerance in agricultural insects to insecticides. The growing demand for chemical pest control necessitates expanding research on the widespread occurrence of cross-tolerance to insecticides among pests, particularly forest pests, in areas polluted with heavy metals. In this study, Cd pre-exposure enhanced the cross-tolerance of Lymantria dispar larvae to β-cypermethrin. Cd pre-exposure activated the P450 detoxification system of L. dispar larvae. CYP6AB224 and CYP6AB226 were key detoxify genes to the formation of cross-tolerance. ROS-CnCC signaling pathway was proved to be responsible for activation of detoxify genes.

CAS / MDL: 51-03-6
研究领域: 环境科学 · 昆虫学 · 分子生物学 · 毒理学
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Acta Biomaterialia · 2021 · IF 8.947

ROS-responsive fluorinated polyethyleneimine vector to co-deliver shMTHFD2 and shGPX4 plasmids induces ferroptosis and apoptosis for cancer therapy

Suleixin Yang,Ka Hong Wong,Peng Hua,Chengwei He,Hua Yu,Dan Shao,Zhi Shi,Meiwan Chen

Ferroptosis is a newly discovered non-apoptotic cell death form but its therapeutic efficacy triggered by traditional iron-based nanomaterials or classic drug inducers has been far from satisfactory due to the high glutathione (GSH) level in cancer cells and insufficient lipid peroxide production. Here we reported a ferroptosis/apoptosis combinational therapy by depleting GSH and downregulating GPX4 to disrupt redox homeostasis and amplify ferroptosis-related oxidation effect. In this study, we developed reactive oxygen species (ROS)-responsive serum-resistant nanoparticles with thioketal-crosslinked fluorinated polyethyleneimine 1.8K ( TK PF) as the core, which were wrapped with hyaluronic acid (HA) as the shell ( TK PFH NP) to co-deliver shGPX4 and shMTHFD2 plasmids for cancer treatment. The highly efficient and tumor-selective gene carrier TK PFH NPs revealed outstanding transfection efficiency (∼100 %) and sustained the efficiency (∼50 %) even in media containing 90 % FBS. Mediated by HA, TK PFH NPs actively targeted CD44 receptors, thus enabling efficient uptake by tumor cells and experiencing surface charge conversion to induce subsequent lysosomal escape. Then the TK PF NPs were effectively disintegrated by the abundant ROS in cancer cells, which facilitated the release of plasmids and avoided the cytotoxicity of cationic polymers. shGPX4 plasmid induced ferroptosis by producing ROS and lipid peroxides via downregulating GPX4, while shMTHFD2 triggered apoptosis by modulating NADPH/NADP and depleting GSH of the cancer cells. Moreover, GSH consumption caused by shMTHFD2 indirectly suppressed GPX4 and further augmented ferroptosis, showing synergistic anticancer effect against B16-F10 cells. Taken together, the rationally designed dual-gene loaded TK PFH NPs provided a safe and high-performance platform for enhanced ferroptosis-apoptosis combined anticancer efficacy based on gene therapy. Statement of significance The therapeutic efficacy of ferroptosis has been far from satisfactory due to high GSH level and insufficient lipid peroxide production in cancer cells. Herein, we reported a ferroptosis/apoptosis combinational therapy by depleting GSH and downregulating GPX4 to disrupt redox homeostasis and amplify ferroptosis-related oxidation effect. ROS-responsive serum-resistant nanoparticles were fabricated with thioketal-crosslinked fluorinated PEI 1.8K ( TK PF) as the core and hyaluronic acid (HA) as the shell ( TK PFH NP) to co-deliver shGPX4 and shMTHFD2 plasmids. The shGPX4 plasmid induced ferroptosis by producing ROS and lipid peroxides via downregulating GPX4, while shMTHFD2 triggered apoptosis by modulating NADPH/NADP and depleting GSH. The rationally designed dual-gene loaded TK PFH NPs provided a safe and high-performance platform aimed for enhanced ferroptosis-apoptosis combined anticancer efficacy.

研究领域: 癌症治疗 · 纳米技术 · 基因递送 · 生物医学工程 · 细胞生物学
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BIOMATERIALS · 2019 · IF 10.273

ROS-responsive polyurethane fibrous patches loaded with methylprednisolone (MP) for restoring structures and functions of infarcted myocardium in vivo

Yuejun Yao,Jie Ding,Zhaoyi Wang,Haolan Zhang,Jieqi Xie,Yingchao Wang,Liangjie Hong,Zhengwei Mao,Jianqing Gao,Changyou Gao

Reactive oxygen species (ROS) play an important role in the pathogenesis of numerous diseases including atherosclerosis, diabetes, inflammation and myocardial infarction (MI). In this study, a ROS-responsive biodegradable elastomeric polyurethane containing thioketal (PUTK) linkages was synthesized from polycaprolactone diol (PCL-diol ), 1,6-hexamethylene diisocyanate (HDI), and ROS-cleavable chain extender . The PUTK was electrospun into fibrous patches with the option to load glucocorticoid methylprednisolone (MP), which were then used to treat MI of rats in vivo . The fibrous patches exhibited suitable mechanical properties and high elasticity. The molecular weight of PUTK was decreased significantly after incubation in 1 mM H 2 O 2 solution for 2 weeks due to the degradation of thioketal bonds on the polymer backbone . Both the PUTK and PUTK/MP fibrous patches showed good antioxidant property in an oxidative environment in vitro . Implantation of the ROS-responsive polyurethane patches in MI of rats in vivo could better protect cardiomyocytes from death in the earlier stage (24 h) than the non ROS-responsive ones. Implantation of the PUTK/MP fibrous patches for 28 days could effectively improve the reconstruction of cardiac functions including increased ejection fraction , decreased infarction size, and enhanced revascularization of the infarct myocardium.

CAS / MDL: 920-66-1
研究领域: 生物材料 · 心脏病学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL POLLUTION · 2023 · IF 8.9

Environment-relevant concentrations of cadmium induces necroptosis and inflammation; baicalein maintains gill homeostasis through suppressing ROS/ER stress signaling in common carps (Cyprinus carpio L.)

Xiaojing Li,Qian Wu,Dan Chen,Yichen Bai,Yuhong Yang,Shiwen Xu

Cadmium (Cd) is a major contaminant in natural environments and exerts adverse effects on aquatic biota at low concentrations. Gill is as vital respiratory organ and may cause pollutants to enter fish during gas exchange. Baicalein (BAI), as a kind of flavonoids, possess antioxidant properties through inactivating free radicals. To confirm the potential effects and approaches of BAI addition in maintaining the gill stability, 90 common carps ( Cyprinus carpio L.) were selected and randomly divided into water environment exposure group (0.22 mg/L Cd) and/or feed added with 0.10 g/kg BAI for 30 days. The analysis of ion content in serum showed that Cd exposure disturbed ion homeostasis , and BAI could reduce serum Cd concentration. The histopathological results of gills showed that Cd exposure caused gill tissue lesions and structural damage, and BAI feeding effectively alleviated this damage. In addition, BAI could enhance antioxidant activity and activate Nrf2/HO-1 axis, thereby reducing oxidative stress and endoplasmic reticulum (ER) stress. Moreover, BAI lightened cytokine imbalance, inflammatory response, and necroptosis. Overall, the results indicated that BAI feeding could maintain gill homeostasis against Cd poisoning via the ROS/ER stress signaling. This trial revealed the properties of BAI resistance to metal Cd in aquaculture and partially elucidated its mechanism.

CAS / MDL: 2921-88-2
研究领域: 水生毒理学 · 环境科学 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Food Packaging and Shelf Life · 2024 · IF 8.5

Bandgap-level engineered photodynamic antibacterial film with boosting ROS production for long-term fruit preservation

Bangfeng Fu,Liang Zhang,Peng Zhao,Weijie Gong,Linpin Luo,Bingzhi Li,Xiaoyue Yue,Jianlong Wang,Yiping Chen

The growing demands for fruit preservation have inspired researchers to concentrate on developing advanced food packaging films with sustained and efficient antimicrobial properties. Herein, a visible light-powered photodynamic antimicrobial packaging system with enhanced reactive oxygen species (ROS) production capability (Bi/BiOI 1-x -CS) was developed by demand-driven engineering of the bandgap structure of the photo-responsive filler (Bi/BiOI 1-x ) and the ingenious selection of chitosan matrix (CS) with bacteria capture and killing capabilities. This film displayed excellent photocatalytic killing performance against Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ) under the visible light, with the bactericidal efficiency up to 99.36 % and 99.54 %, respectively. The enhancement stemmed from the reasonable optimization of the following two aspects: (i) The iodine defects and lateral modification of pure bismuth jointly optimized the electronic band structure of BiOI and significantly boosted the ROS production level, and (ii) The capturing characteristic of CS on bacteria might shorten the diffusion distance between ROS and bacteria, thus further amplifying the bactericidal effect of ROS. As a result, the as-prepared Bi/BiOI 0.20 1-x -CS film (0.20 shows the Bi/BiOI 1-x amount in film solution) exhibited enhanced preservation ability, significantly extending the shelf life of kumquats from 18 to 27 days. Meanwhile, the introduction of Bi/BiOI 1-x successfully promoted the mechanical properties, ultraviolet-barrier performance, and hydrophobicity of CS film. The enhancement of comprehensive performance underscores the potential application of Bi/BiOI 1-x -CS film in the field of fruit preservation.

研究领域: 材料科学 · 食品科学 · 纳米技术 · 生物技术 · 环境科学
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ACS Omega · 2024 · IF 3.7

Dynamic-Covalent Mesoporous Silica Nanohybrid with pH/ROS-Responsive Drug Release for Targeted Tumor Therapy

Yurong Leng,Yanmei Wu,Wenjing Xiao,Xiaoquan Su,Zhe Liu

Nanomedicine provides promising new methodologies for the treatment of tumors but still faces several limitations, including poor colloidal stability, uncontrollable drug release, and insufficient drug targeting. Herein, hyaluronic acid (HA) was used to modify the surface of mesoporous silica nanoparticles (MSNs) via a dynamic-covalent linker, phenylborate ester (PBAE), termed MA. The HA modifier provided enhanced colloidal stability to the hybrid nanoparticles. As expected, MA exhibited an improved biocompatibility and high potential for biomedical applications. Moreover, MA with a negatively charged surface effectively adsorbed the drug Doxorubicin (DOX) inside the carriers, ensuring minimal drug leakage. In an acidic and reactive oxygen species (ROS)-containing condition mimicking the tumor microenvironment, MA@DOX (MAD) continuously released its payloads, likely due to the cleavage of the pH/ROS-sensitive PBAE. Compared with free DOX, MAD had 2.2 times higher accessibility to tumor cells than free DOX. The favorable stability and cancer-selective drug release make this nanoformulation a promising platform for potent cancer treatment.

CAS / MDL: 14047-29-1 67-68-5
研究领域: 纳米医学 · 药学 · 癌症治疗 · 材料科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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