ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Beibei Zhang,Hao Liu,Yifei Wang,Yong Zhang
Ferroptosis is an appealing cancer therapy strategy based on the H2O2-involved Fenton reaction to produce toxic •OH for lipid peroxidation. However, intracellular H2O2 is easily consumed and results in a deficient Fenton reaction. This obstacle can be overcome by traditional chemotherapeutic drugs for H2O2 supplements. Moreover, a recent work illustrated that dihydroartemisinin (DHA) could promote ferroptosis against tumoral cells, particularly in the presence of ferrous compounds. To achieve combined chemotherapy and ferroptosis, a nanocarrier (TKNPDHA-Fc) was constructed by using thioketal (TK)-bridged paclitaxel prodrug (PEG-TK-PTX) and ferrocene (Fc)-conjugated PEG-Fc, where DHA was encapsulated by a hydrophobic–hydrophobic interaction. Upon cellular uptake, TKNPDHA-Fc could facilitate PTX release through TK breakage under an excess H2O2 microenvironment. Owing to the loss of the hydrophobic PTX component, TKNPDHA-Fc underwent a rapid dissociation for improving DHA to act as a ferroptotic inducer along with Fe supplied from Fc. Moreover, both the chemotherapy-induced reactive oxygen species and the •OH produced from reinforced ferroptosis further stimulated the TK cleavage. The “self-catalytic” loop of TKNPDHA-Fc remarkably improved the antitumor performance in vivo via combined mechanisms, and its tumor inhibition rate reached 78.3%. This work highlights the contribution of ROS-responsive and self-catalytic nanoplatforms for enhancing the potential of combined chemotherapy and ferroptosis for cancer therapy in the future.
研究领域:
癌症治疗
·
纳米技术
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Liang Qi,Bo-Wen Duan,Hui Wang,Yan-Jun Liu,Han Han,Meng-Meng Han,Lei Xing,Hu-Lin Jiang,Stephen J. Pandol,Ling Li
Pancreatic fibrosis (PF) is primarily characterized by aberrant production and degradation modes of extracellular matrix (ECM) components, resulting from the activation of pancreatic stellate cells (PSCs) and the pathological cross-linking of ECM mediated by lysyl oxidase (LOX) family members. The excessively deposited ECM increases matrix stiffness, and the over-accumulated reactive oxygen species (ROS) induces oxidative stress, which further stimulates the continuous activation of PSCs and advancing PF; challenging the strategy toward normalizing ECM homeostasis for the regression of PF. Herein, ROS-responsive and Vitamin A (VA) decorated micelles (named LR-SSVA) to reverse the imbalanced ECM homeostasis for ameliorating PF are designed and synthesized. Specifically, LR-SSVA selectively targets PSCs via VA, thereby effectively delivering siLOXL1 and resveratrol (RES) into the pancreas. The ROS-responsive released RES inhibits the overproduction of ECM by eliminating ROS and inactivating PSCs, meanwhile, the decreased expression of LOXL1 ameliorates the cross-linked collagen for easier degradation by collagenase which jointly normalizes ECM homeostasis and alleviates PF. This research shows that LR-SSVA is a safe and efficient ROS-response and PSC-targeted drug-delivery system for ECM normalization, which will propose an innovative and ideal platform for the reversal of PF.
研究领域:
药理学
·
纳米技术
·
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
Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Kaili Liang,Li Yang,Jiawei Kang,Bo Liu,Ding Zhang,Liyan Wang,Wei Wang,Qing Wang
Parkinson's disease (PD) poses a significant therapeutic challenge, mainly due to the limited ability of drugs to cross the blood-brain barrier (BBB) without undergoing metabolic transformations. Levodopa, a key component of dopamine replacement therapy, effectively enhances dopaminergic activity. However, it encounters obstacles from peripheral decarboxylase, hindering its passage through the BBB. Furthermore, levodopa metabolism generates reactive oxygen species (ROS), exacerbating neuronal damage. Systemic pulsatile dosing further disrupts natural physiological buffering mechanisms. In this investigation, we devised a ROS-responsive levodopa prodrug system capable of releasing the drug and reducing ROS levels in the central nervous system. The prodrug was incorporated within second near-infrared region (NIR-II) gold nanorods (AuNRs) and utilized angiopep-2 (ANG) for targeted delivery across the BBB. The processes of tight junction opening and endocytosis facilitated improved levodopa transport. ROS scavenging helped alleviate neuronal oxidative stress, leading to enhanced behavioral outcomes and reduced oxidative stress levels in a mouse model of PD. Following treatment, the PD mouse model exhibited enhanced flexibility, balance, and spontaneous exploratory activity. This approach successfully alleviated the motor impairments associated with the disease model. Consequently, our strategy, utilizing NIR-Ⅱ AuNRs and ANG-mediated BBB penetration, coupled with the responsive release of levodopa, offers a promising approach for dopamine supplementation and microenvironmental regulation. This system holds substantial potential as an efficient platform for delivering neuroprotective drugs and advancing PD therapy.
研究领域:
神经科学
·
药理学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 11
·2965-2975
·
IF 5.831
Bin Yang,Kaiyuan Wang,Dong Zhang,Bingjun Sun,Bin Ji,Lin Wei,Zhenbao Li,Menglin Wang,Xuanbo Zhang,Haotian Zhang,Qiming Kan,Cong Luo,Yongjun Wang,Zhonggui He,Jin Sun
In the context of prodrug nanomedicines for cancer therapy, one of the great challenges is the slow and variable release of the parent drug in tumors. Recently, many smart redox-sensitive nanocarriers have been developed to address this problem. However, due to significant tumor heterogeneity, some redox-sensitive nanomedicines still show poor selectivity in drug release. Herein, we report the design and synthesis of a ROS-triggered prodrug nanoplatform fabricated with oxidation-responsive cabazitaxel (CTX) prodrugs for synergistic chemo-photodynamic therapy, thioether-/selenoether-linked conjugates of CTX and oleic acid (OA). These prodrugs can be readily self-assembled into nanoparticles, with pyropheophorbide a (PPa) co-encapsulated into the prodrug-nanosystem for combination therapy. The dual-source ROS-responsive prodrug nanosystems selectively and rapidly release CTX not only in response to endogenous ROS overproduced in tumor cells, but also to exogenous PPa-generated ROS under laser irradiation. Moreover, the selenium-containing linkage demonstrates significant advantages over a sulfur-containing linkage in terms of ROS-triggered drug release and cytotoxicity. The prepared prodrug-nanosystems significantly prolong the systemic circulation and tumor distribution of both CTX and PPa, thereby demonstrating synergistic chemo-photodynamic therapy in vivo. All these drug delivery advantages render the nanosystem extremely promising for cancer treatment.
研究领域:
癌症治疗
·
纳米医学
·
药学科学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Yu Xia,Runhai Chen,Ye Ke,Qiaoyi Han,Zhifang Ma,Qiang Shi
Inflammatory and thrombotic complications, and low loading of dual drugs with different hydrophilicity remain challenges to treat thrombosis with drug delivery systems (DDS). Here, the reactive oxygen species (ROS)-responsive amphiphilic block polymer poly(ethylene glycol)-b-2-((((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl)oxy)carbonyl)oxy)ethyl methacrylate (PEG-b-PTBEM) is synthesized. And the nanovesicles (PPTV) are prepared successfully for the drug delivery platform by controlling the hydrophilic/hydrophobic ratio of molecular chains and molecular self-assembly. The anti-inflammatory drug indomethacin (IDM) is loaded in the wall of nanovesicels and the thrombolytic enzyme nattokinase (NK) is encapsulated in the aqueous cavity of nanovesicles. Both drugs can be rapidly released in the site of thrombus and/or inflammation with excessive ROS concentration. The dual drug-loaded nanovesicles not only eliminate ROS, but also alleviate inflammation and dissolve generated thrombus, showing significant therapeutic efficacy in the in-vivo mouse model of carrageenan tail thrombosis. Therefore, drug-delivery nanovesicles play multiple roles in the treatment of inflammation-induced thrombotic disorders, which offers a promising treatment for inflammatory and thrombotic complications.
研究领域:
药学
·
纳米技术
·
治疗学
·
药物递送系统
·
炎症
·
血栓
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Xuan Li,Kun Xu,Ye He,Bailong Tao,Ke Li,Chuanchuan Lin,Jingwei Hu,Jing Wu,Yi Wu,Shaopeng Liu,Peng Liu,Huaiyu Wang,Kaiyong Cai
Ideal titanium implants are required to participate in bone repair actively to improve in situ osteointegration. However, the traditional surface functionalization methods of titanium implants are difficult to both achieve the active regulation and long-term stability of bioactive components. Here, a novel functionalized titanium which loaded with thymosin β4 (Tβ4) and covered by a hydrogel coating was designed and evaluated. A strong adhesion between the coating and the titanium substrate was realized by the synergistic action of borate ester bonds and surface topological structure. The hydrogel coating also achieved an in vivo adhesion between implant and tissue through hydrogen bonds and borate bonds. In addition, based on the ROS response property of borate bonds, the implant can release Tβ4 in response to the immune reaction of bone healing by regulating the polarization of macrophages, thereby reducing the fibrosis formation around the implant interface and promoting vascularization and osteointegration of bone defects.
研究领域:
生物材料
·
组织工程
·
免疫学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Zhidong Lin,Luoqi Mai,Huitong Luo,Zetao Wang,Yongpeng Lin,HongShen Wang,Shaohua Chen,Guoyi Su,Xulin Hu,Bolai Chen,Xiaodong Cao
Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain, characterized by the ferroptosis of nucleus pulposus cells (NPCs) and imbalance in reactive oxygen species (ROS) metabolism. Icariin (ICA), an active compound from traditional Chinese medicine, scavenges ROS and inhibits ferroptosis, but its poor water solubility and low bioavailability limit clinical use. A dual-crosslinked hydrogel (HP@ICA) is developed to address these challenges. Cyclodextrin is integrated into polyvinyl alcohol to enhance ICA loading via hydrophobic interactions. Methacrylic acid and phenylboronic acid are incorporated into hyaluronic acid, enabling dynamic bonding with polyvinyl alcohol. Ultraviolet crosslinking creates a secondary crosslinked hydrogel with pH and ROS responsiveness, self-healing properties, and improved ICA solubility, increasing its water solubility tenfold. Enhanced solubility boosts ICA's free radical scavenging capacity by 103 %, suppressing ferroptosis and promoting NP cell regeneration, as demonstrated by reduced iron ion concentrations, lower malondialdehyde levels, and restored glutathione peroxidase 4 activity. Ferroptosis inhibition facilitates type II collagen production in NP cells. Mechanistic studies reveal activation of the Nrf2-GPX4 pathway as key to regeneration. These findings suggest a promising regenerative therapeutic approach for IVDD.
研究领域:
生物医学工程
·
再生医学
·
药剂纳米技术
·
骨科
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Li Xiaoqun,Kou Yufang,Jia Jia,Liu Minchao,Gao Runze,Li Yuhong,Li Gang,Xu Shuogui,Song Wei,Xie Yang,Li Xiaomin,Zhao Tiancong
The excessive reactive oxygen species (ROS) accumulation and overactivated osteoclastogenesis in subchondral bone has proved to be a major cause of osteoarthritis (OA). Scavenging of ROS microenvironment to inhibit the osteoclastogenesis is highly valued in the therapeutic process of osteoarthritis. Despite the excellent ability of polyphenolic colloidal to scavenge reactive oxygen species and its affinity for macrophages, the preparation of polyphenolic colloidal nanoparticles is limited by the complex intermolecular forces between phenol molecules and the lack of understanding of polymerization/sol-gel chemistry. Herein, our work introduces a novel poly-tannin-phenylboronic colloidal nanoparticle (PTA) exclusively linked by ROS-responsive bondings. Nanocolloidal PTA has a uniform particle size, is easy and scalable to synthesize, has excellent scavenging of ROS, and can be slowly degraded. For in vitro experiments, we demonstrated that, PTA could eliminate ROS within RAW264.7 cells and impede osteoclastogenesis and bone resorption. RNA sequencing results of PTA-treated RAW264.7 cells further reveal the promotion of antioxidant activity and inhibition of osteoclastogenesis. For in vivo experiments, PTA could eliminate the ROS environment and reduce the number of osteoclasts in the subchondral bone, thereby alleviating the damage of subchondral bone and symptoms of osteoarthritis. Our research, by delving into the formation of polyphenol colloidal nanoparticles and validating their role in ROS scavenging to inhibit osteoclastogenesis in subchondral bone, may open new avenues for OA treatment in the future.
研究领域:
纳米技术
·
生物材料
·
骨科
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Wajiha Ahmed,Shifen Li,Min Liang,Yongyuan Kang,Xiaoqing Liu,Changyou Gao
Elevated levels of ROS, bacterial infection, inflammation, and improper regeneration are the factors that need to be addressed simultaneously for achieving effective wound healing without scar formation. This study focuses on the fabrication of electrospun ROS-responsive selenium-containing polyurethane nanofibers incorporating deferoxamine mesylate (Def), indomethacin (Indo), and gold nanorods (AuNRs) as proangiogenesis, anti-inflammatory, and antibacterial agents for synchronized delivery to a full-thickness wound in vivo. The structure of the fabricated nanofibers was analyzed by various techniques. Toxicity was checked by CCK-8 and hemolytic assays. The efficiency of wound healing in vitro was verified by a transwell assay and cell scratch assay. The wound healing efficiency of the nanofibers was assayed in full-thickness wounds in a rat model. The multifunctional nanofibers had a porous structure, enhanced antioxidation, antibacterial activity, and promoted wound healing. They eradicated TNF-α and IL-6, increased IL-10 expression, and revealed the angiogenic potential by increased expression of HIF-1α, VEGF, and CD31.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PARTICLE & PARTICLE SYSTEMS CHARACTERIZATION
·
2020
·Vol. 37
·期 5
·2000021
·
IF 3.099
Ali Maruf,Yi Wang,Li Luo,Yuan Zhong,Deti Nurhidayah,Boyan Liu,Dan Tang,Muhammad Abdul Rouf,Haijun Zhang,Yuxia Yin,Wei Wu,Guixue Wang
The development of smart nanoagents that can respond to a specific stimulus has gained remarkable interest for treating various kinds of diseases, including atherosclerosis. On the other hand, a cell camouflaging strategy has been considered as a pivotal factor to improve the delivery stealthiness, biocompatibility, and biodegradability of nanocarriers, resolving the shortcomings of PEGylation. In this study, reactive oxygen species (ROS)-responsive 5-aminolevulinic acid (ALA) prodrug nanostructures (ROSELLA) encapsulating rapamycin (RAP) are blended with nanoerythrocyte membranes to construct red blood cell membrane (RBCM)/RAP@ROSELLA. These nanoagents are designed to be able to escape the biological barriers, accumulate in atherosclerosis lesions, and enhance the release of drugs in the intracellular milieu due to the magnification of hydrogen peroxide (H 2 O 2 ). In vitro study proves its superior ability to inhibit the proliferation of macrophages and vascular smooth muscle cells. In vivo developmental toxicity further confirms that no significant systematic toxicity is induced by RBCM/RAP@ROSELLA, implying its favorable biocompatibility, which has potential for precise nanomedicine to combat atherosclerosis.
研究领域:
纳米技术
·
药学
·
心血管疾病
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2022
·
IF 8.025
Yi Li,Chunjing Guo,Qiang Chen,Yanguo Su,Huimin Guo,Ruoyang Liu,Changgang Sun,Shuqi Mi,Jinqiu Wang,Daquan Chen
Pneumonia can lead to high morbidity and mortality secondary to uncontrolled inflammation of the lung tissue. Blocking cytokine storm storms may be the key to saving the life of patients with severe pneumonia. According to the medicinal guide theory of Traditional Chinese Medicine (TCM) and the inherent affinity with macrophages for the site of inflammation, we constructed the drug delivery platform (MNPs) derived from macrophage-membrane encapsulated reaction oxygen species (ROS)-responsive Platycodon grandiflorum polysaccharides (PGP) nanoparticles (PNPs) to calm the cytokine storm and improve lung inflammation. By loading the anti-inflammatory agent Curcumin (Cur), we demonstrated that [email protected] significantly attenuated inflammation and cytokine storm syndrome in acute lung injury (ALI) mice by suppressing pro-inflammatory factor production and inflammatory cell infiltration. Interestingly, we observed that the PNPs also have potent pulmonary targeting ability compared to other polysaccharide carriers, which is in line with the medicinal guide theory of TCM. Our study revealed the rational design of drug delivery platforms to improve the treatment of lung injury, which inherits and develops the important theories of TCM through the perfect combination of guide theory and biomimetic nanotechnology and provides the experimental scientific basis for the clinical application of channel ushering drugs.
研究领域:
药理学
·
纳米技术
·
中医
·
免疫学
·
肺科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SUPERCRITICAL FLUIDS
·
2022
·
IF 4.514
Jin-Zhou Rui,Hu-Hong Peng,Yi-Xin Guan,Shan-Jing Yao
Drug-loaded hydrogels with wound environment stimuli-responsive property can significantly promote wound healing and are widely applied in dressings. Two natural polymers , i.e. sodium alginate and sodium hyaluronate , were modified by 3-aminophenylboric acid and then cross-linked with polyvinyl alcohol to prepare ROS responsive hydrogels. Doxycycline hydrochloride was loaded onto hydrogels using supercritical solvent impregnation (SSI) technology, and the effects of immersion time, pressure and temperature on drug loading capacity (DLC) were investigated. DLC firstly increased and then decreased with the elevation of supercritical CO 2 pressure, and maximum value was up to 11 mg/g at 15 MPa and 50 °C. In the in vitro drug release study, doxycycline hydrochloride was controllably released from hydrogels for 10 h via the sensitivity of boronate ester bonds to ROS. This work expands the application of SSI in wound dressing, which provides a new approach for the design of composite hydrogel formulations with uniform drug distribution.
研究领域:
材料科学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）