JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Zishan Zeng,Yong Luo,Xiaoyu Xu,Ting Shan,Meixu Chen,Zeqian Huang,Yanjuan Huang,Chunshun Zhao
Mitochondrion is an ideal target for amplifying ROS attack in antitumor treatment. Benefiting from distinctive properties of mitochondria, the precise delivery of ROS generator to mitochondria could maximumly utilize ROS for oxidation therapy. Herein, we prepared an innovative ROS-activatable nanoprodrug (HTCF) which dually targets tumor cells and mitochondria for antitumor therapy. Cinnamaldehyde (CA) was conjugated to ferrocene (Fc) and triphenylphosphine by thioacetal linker, to synthesize mitochondria-targeting ROS-activated prodrug (TPP-CA-Fc), which subsequently self-assembled into nanoprodrug via host-guest interactions between TPP-CA-Fc and cyclodextrin-decorated hyaluronic acid conjugate. Under mitochondrial high ROS condition, especially in tumor cells, HTCF selectively initiate in-situ Fenton reaction to catalyze H 2 O 2 into highly cytotoxic •OH, ensuring maximum generation and utilization of •OH for precision CDT. Meanwhile, the mitochondrial high ROS trigger thioacetal bond cleavage and CA release. The released CA stimulate mitochondrial oxidative stress aggravation and H 2 O 2 regeneration, which in turn react with Fc for more •OH generation, forming self-amplifying positive feedback cycle of CA release and ROS burst. With self-augmented Fenton reaction and mitochondria-specific destruction, HTCF ultimately induce intracellular ROS burst and severe mitochondrial dysfunction for amplified ROS-mediated antitumor therapy. Such an ingenious organelles-specialized nanomedicine exhibited prominent antitumor effect both in vitro and in vivo, revealing underlying perspectives to amplify tumor-specific oxidation therapy.
研究领域:
药学
·
纳米技术
·
肿瘤学
·
化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·
IF 13.3
Yang Zhou,Yiwei Zhang,Chaoqing Jiang,Yuxiu Chen,Fan Tong,Xiaotong Yang,Yazhen Wang,Xue Xia,Huile Gao
A primary concern about photodynamic therapy (PDT) is its inability to regulate the generation levels of reactive oxidative species (ROS) based on the complex microenvironment, resulting in the impairment toward normal tissues and immunosuppression. Besides, tumor metastasis also compromises PDT's efficacy and drives mortality. However, it is very challenging to achieve such two goals within one nanosystem. Here, the nanoassembly (CPR) with self-regulated photodynamic and antimetastasis properties comprises three parts: chlorin e6-conjugated β-cyclodextrin (CD-Ce6) acts as the main PDT agent and ferrocene (Fc)-terminated phenylboronic acid-containing conjugates entering into the cavity of CD-Ce6, as well as rosmarinic acid (RA)–boronic acid crosslinked shell. Compared with non-crosslinked counterpart, CPR displays better stability and enhanced tumor accumulation. Under laser irradiation, CPR generates plenty of ROS to damage tumor cells and induce immunogenic cell death. Mildly acidic TME partly cleaves the crosslinkers to dissociate antioxidant RAs from micelles, which together with Fc in CPR scavenge PDT-induced ROS in the TME. By contrast, under acidic lysosomal conditions, Fc catalyzes abundant H 2 O 2 in tumor cells to produce highly cytotoxic •OH, while RA continuously reduces ferroptosis-generated Fc + into Fc, both to augment the PDT efficacy in tumor cells. CPR also remarkably hinders the epithelial-mesenchymal transition to prevent the lung metastasis.
研究领域:
纳米技术
·
癌症研究
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Yufei Cao,Mingsheng Liu,Ju Cheng,Juanjuan Yin,Congshu Huang,Haiyan Cui,Xiangdong Zhang,Guanghui Zhao
Nitric oxide (NO) gas therapy has aroused intense interest in recent years. l-Arginine (l-Arg) reacts with reactive oxygen species (ROS) in tumor cells to generate NO. This phenomenon represents an effective method for tumor therapy. However, endogenous ROS levels in most types of tumor cells cannot enable an effective reaction. β-Lapachone is generally used to increase H2O2, which can oxidize guanidine derivatives to form nitric oxide in tumor cells. In addition, based on the ferrocene (Fc)-catalyzed Fenton reaction, ·OH is generated from H2O2, and the ONOO– could be generated from an interaction between ·O2– (generated through the Haber–Weiss reaction) and NO. Arg-rich poly(ε-caprolactone) (PCL)-b-PArg, a macromolecular NO donor, was accurately synthesized to avoid premature l-Arg leakage during in vivo transport. In this design, the self-assembled PCL-b-PArg nanoparticles were dressed with the tumor-shreddable masking (PEG-b-PDMA, a negatively charged pH-sensitive hydrophilic diblock polymer), to prepare P-lapa-Fc nanoparticles and hide penetrative capability in the circulation. The experimental results confirmed that this synergistic therapy based on ROS and NO had a significant inhibitory effect on cancer cells, thereby providing new inspiration for NO gas treatment.
研究领域:
癌症治疗
·
纳米医学
·
药物化学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Wenwen Xue,Zilian Jiang,Yahui Wang,Hongfang Zhang
Sensitive and accurate detection of tumor suppressor genes is vastly important to the related therapeutic research. Herein, a ratiometric electrochemical method for let-7a detection was established by integrating a ferrocene (Fc) doped MoS 2 nanoplates modified electrode into the nanochannels-based biosensing platform. The ratiometric signal was developed by the redox current of methylene blue (MB) which reflects the target recognition occurred into the nanochannels and the redox current of Fc which corrects the slight signal deviation caused by some analyte-independent factors. And thus, the ratio of peak current of MB and Fc ( I MB / I Fc ) measured at differential pulse voltammogram varied precisely with the increment of the concentration of let-7a incubated in the bioinspired nanochannels. The strategy of spherical DNAzyme induced deposition in nanochannels was utilized to further amplify the signal. Under optimal conditions, a wide linear dynamic range of 50 aM to 10 pM spanning five orders of magnitude was obtained. The developed electrochemical method, with attomole level of detection limit, was successfully applied to the determination of let-7a in human serum and tumor cells. The study not only offers a new route for reliable nucleic acid detection, but also provides an excellent opportunity to extend the application of the two-dimensional transition-metal dichalcogenides.
研究领域:
生物化学
·
纳米技术
·
电化学
·
癌症研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Min Tan,Jing Zeng,Fu-Zhong Zhang,Ye-Tao Zhang,Hongli Li,Shu-Ting Fan,Jia-Xin Wang,Minglong Yuan,Bang-Jing Li,Sheng Zhang
Slow healing of wounds induces great pain in diabetic patients. However, developing new approaches to promote diabetic wound healing is still one of the toughest challenges in the medical field. Here, we constructed a new double-layer hydrogel to effectively regulate reactive oxygen species (ROS) on the wound and promote diabetic wound healing. The inner layer contains glucose oxidase (Gox), ferrocene-modified quaternary ammonium chitosan (Fc-QCs), and poly(β-cyclodextrin) (Pβ-CD), which is used to generate hydroxyl radicals (•OH) for antibacterial in the early stage of wound healing and collapses gradually. The outer layer is composed of gelatin and dopamine. In the later stage of wound healing, the outer layer contacts the skin, which is beneficial for ROS clearance on the wound. Antibacterial, ROS scavenging, and wound healing experiments have shown that the double-layer hydrogel possesses two-stage ROS regulating properties for programmed diabetic wound healing. In conclusion, it will be one of the most potential dressings for treating diabetic wounds in the future.
研究领域:
材料科学
·
生物医学工程
·
伤口愈合
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2022
·
IF 4.831
Xinhui Hou,Yifan Song,Yupeng Lv,Peiyao Wang,Kun Chen,Guiying Li,Lei Guo
Temperature-responsive nanomicelles with aggregation induced emission (AIE) property were prepared by the host–guest complexation of ferrocene functionalized tetraphenyl (TPE-Fc) and β-cyclodextrin-poly ( N -isopropylacrylamide) (β-CD-(PNIPAM) 7 ). The AIE chromophore TPE-Fc bound to the hydrophobic cavity of cyclodextrin serves as the core of micelles, and temperature sensitive PNIPAM serves as the shell to give the micelles good solubility. The size of the nanomicelles is about 100 nm. At the excitation wavelength of 340 nm, the strongest fluorescent emission peak was 421 nm. The introduction of cyclodextrin star polymer increased the fluorescence intensity of nanomicelles, thus improving the recognition of probe to Fe 3+ and Fe 2+ . The fluorescent probe can quickly detect Fe 3+ and Fe 2+ in water within 5 min even in the presence of various interfering ions. The detection limits of Fe 3+ and Fe 2+ were 1.04 μM and 0.78 μM, respectively in the range of 10–90 μM. The formation of complex between the probe and Fe 3+ /Fe 2+ was supported by Job’s plot. The probe was successfully applied to the detection of Fe 3+ and Fe 2+ in actual water sample with a good recovery. In addition, a possible sensing mechanism for the interaction of iron ions with amide bond groups of nanomicelles was proposed.
研究领域:
材料科学
·
分析化学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2023
·
IF 7.4
Jia Kong,Shixuan Zhao,Xue Han,Wenxin Li,Jiaxing Zhang,Yuefei Wang,Xihui Shen,Yinqiang Xia,Zhonghong Li
Fluorescent proteins (FPs) provide a ratiometric readout for quantitative assessment of the destination of internalized biomolecules. FP-inspired peptide nanostructures that can compete with FPs in their capacity are the most preferred building blocks for the synthesis of fluorescent soft matter. However, realizing a ratiometric emission from a single peptide fluorophore remains exclusive since multicolor emission is a rare property in peptide nanostructures. Here, we describe a bioinspired peptidyl platform for ratiometric intracellular quantitation by employing a single ferrocene-modified histidine dipeptide. The intensiometric ratio of green to blue fluorescence correlates linearly with the concentration of the peptide by three orders of magnitude. The ratiometric fluorescence of the peptide is an assembly-induced emission originating from hydrogen bonds and aromatic interactions. Additionally, modular design enables ferrocene-modified histidine dipeptides to use as a general platform for the construction of intricate peptides that retain the ratiometric fluorescent properties. The ratiometric peptide technique promises flexibility in the design of a wide spectrum of stoichiometric biosensors for quantitatively understanding the trafficking and subcellular fate of biomolecules.
研究领域:
生物化学
·
纳米技术
·
分子生物学
·
生物物理学
·
分析化学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2019
·
IF 6.35
Hua Chai,Wenbo Cheng,Lei Xu,Huiqiang Gui,Jinlin He,Peng Miao
Herein we describe a novel isothermal and enzyme-free electrochemical aptasensor for protein detection via the employment of polymeric ferrocene nanoparticles (PFcNPs) and target-catalyzed hairpin assembly amplification. The synthesized PFcNPs not only load numerous Fc molecules for enhanced electrochemical output but also possess plenty of amino groups, which increase the water solubility and facilitate the conjugation with the aptamer toward the recognition of target protein. After the formation of an aptamer/protein complex, the conformation of the DNA probe changes, which further triggers hairpin assembly on top of DNA tetrahedral structures modified on the electrode interface. The process can be recycled, and multiple PFcNPs are localized on the electrode. Thus, an amplified electrochemical signal is able to be recorded, which is sufficient to achieve a demonstrated limit of detection as low as 67 fM. This developed aptasensor can also discriminate target protein from other interfering substances with a high selectivity. Furthermore, it has been successfully applied in diluted real blood serum samples. All of these features make the present methodology a promising candidate for ultratrace protein biosensors.
研究领域:
分析化学
·
生物传感器
·
纳米技术
·
电化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Jianhua He,Wenli Zhang,Xiaoju Zhou,Fengfei Xu,Jiahui Zou,Qiqi Zhang,Yi Zhao,Hongliang He,Hu Yang,Jianping Liu
Nanoparticle-based therapeutics represent potential strategies for treating atherosclerosis; however, the complex plaque microenvironment poses a barrier for nanoparticles to target the dysfunctional cells. Here, we report reactive oxygen species (ROS)-responsive and size-reducible nanoassemblies, formed by multivalent host-guest interactions between β-cyclodextrins (β-CD)-anchored discoidal recombinant high-density lipoprotein (NP 3 ST ) and hyaluronic acid-ferrocene (HA-Fc) conjugates. The HA-Fc/NP 3 ST nanoassemblies have extended blood circulation time, specifically accumulate in atherosclerotic plaque mediated by the HA receptors CD44 highly expressed in injured endothelium, rapidly disassemble in response to excess ROS in the intimal and release smaller NP 3 ST , allowing for further plaque penetration, macrophage-targeted cholesterol efflux and drug delivery. In vivo pharmacodynamicses in atherosclerotic mice shows that HA-Fc/NP 3 ST reduces plaque size by 53%, plaque lipid deposition by 63%, plaque macrophage content by 62% and local inflammatory factor level by 64% compared to the saline group. Meanwhile, HA-Fc/NP 3 ST alleviates systemic inflammation characterized by reduced serum inflammatory factor levels. Collectively, HA-Fc/NP 3 ST nanoassemblies with ROS-responsive and size-reducible properties exhibit a deeper penetration in atherosclerotic plaque and enhanced macrophage targeting ability, thus exerting effective cholesterol efflux and drug delivery for atherosclerosis therapy.
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
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Jialin Song,Huan Liu,Miao Lei,Haoqi Tan,Zhanyi Chen,Artem Antoshin,Gregory F. Payne,Xue Qu,Changsheng Liu
Microbial disinfection associated with medical device surfaces has been an increasing need, and surface modification strategies such as antibacterial coatings have gained great interest. Here, we report the development of polydopamine-ferrocene (PDA-Fc)-functionalized TiO2 nanorods (Ti-Nd-PDA-Fc) as a context-dependent antibacterial system on implant to combat bacterial infection and hinder biofilm formation. In this work, two synergistic antimicrobial mechanisms of the PDA-Fc coating are proposed. First, the PDA-Fc coating is redox-active and can be locally activated to release antibacterial reactive oxygen species (ROS), especially ·OH in response to the acidic microenvironment induced by bacteria colonization and host immune responses. The results demonstrate that redox-based antimicrobial activity of Ti-Nd-PDA-Fc offers antibacterial efficacy of over 95 and 92% against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), respectively. Second, the photothermal effect of PDA can enhance the antibacterial capability upon near-infrared (NIR) irradiation, with over 99% killing efficacy against MRSA and E. coli, and even suppress the formation of biofilm through both localized hyperthermia and enhanced ·OH generation. Additionally, Ti-Nd-PDA-Fc is biocompatible when tested with model pre-osteoblast MC-3T3 E1 cells and promotes cell adhesion and spreading presumably due to its nanotopographical features. The MRSA-infected wound model also indicates that Ti-Nd-PDA-Fc with NIR irradiation can effectively eliminate bacterial infection and suppress host inflammatory responses. We believe that this study demonstrates a simple means to create biocompatible redox-active coatings that confer context-dependent antibacterial activities to implant surfaces.
研究领域:
材料科学
·
生物医学工程
·
微生物学
·
表面化学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xiangyan Chen,Tianze Jiang,Yantao Li,Yifei Zhang,Jianqi Chen,Xia Zhao,Hai Yang
The immune-suppressive microenvironment of solid tumors is a key factor limiting the effectiveness of immunotherapy , which seriously threatens human life and health. Ferroptosis and apoptosis are key cell-death pathways implicated in cancers, which can synergistically activate tumor immune responses. Here, we developed a multifunctional composite hydrogel (CE-Fc-Gel) based on the self-assembly of poloxamer 407 , cystamine-linked ιota-carrageenan (CA)-eicosapentaenoic acid (EPA), and ferrocene (Fc). CE-Fc-Gel improved targeting in tumor microenvironment due to its disulfide bonds . Moreover, CE-Fc-Gel promoted lipid peroxidation, enhanced reactive oxygen species (ROS) production, and decreased glutathione peroxidase 4 (GPX4), inducing ferroptosis by the synergistic effect of Fc and EPA. CE-Fc-Gel induced apoptosis and immunogenic cell death (ICD), thereby promoting dendritic cells (DCs) maturation and T cell infiltration. As a result, CE-Fc-Gel significantly inhibited primary and metastatic tumors in vivo. Our findings provide a novel strategy for enhancing tumor immunotherapy by combining apoptosis, ferroptosis, and ICD.
研究领域:
肿瘤学
·
免疫疗法
·
材料科学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Xiaoyu Xu,Zishan Zeng,Jie Chen,Binyao Huang,Zilin Guan,Yanjuan Huang,Zeqian Huang,Chunshun Zhao
Utilizing intratumoral iron mediated Fenton reaction to induce cancer cells destruction, chemodynamic therapy (CDT) is an emerging tumor-specific therapeutic strategy. However, the CDT efficacy is severely restrained by insufficient endogenous H 2 O 2 and catalytic ferrous ions in tumor site. Herein, based on innovative small molecule prodrug design concept, an acid-labile ferrocene-modified cinnamaldehyde prodrug (Fc-CA) was first synthesized. Skillfully combining ROS-generator CA with Fenton catalyst Fc in its molecular structure, Fc-CA could synchronously elevate H 2 O 2 level and catalytic iron amount for enhanced CDT efficacy. Then, hydrophobic Fc-CA was efficiently encapsulated into hydrophilic cyclodextrin-modified hyaluronic acid conjugate (HA-CD) via host-guest interactions, to spontaneously form pH/redox dual-responsive supramolecular catalytic nanoreactor (HA-CD/Fc-CA NPs). The nanoreactor with high drug loading and stability, excellent catalytic activity and tumor specificity could preferentially accumulate in tumor tissues via EPR effect and CD44 receptor-mediated internalization. Through the cleavage of acid-labile hydrazone bond under acidic lysosome environments, the nanoreactor would be dissociated and release pre-protected CA for reinforced oxidation therapy and amplified H 2 O 2 level, which would in turn react with Fc through cascaded Fenton reaction, to generate highly cytotoxic •OH for enhanced cancer killing in a positive feedback process. Both in vitro and in vivo results verified excellent cascade-amplifying therapeutic performance and favorable biocompatibility of this nanoreactor. This study provides an innovative strategy for exploiting versatile organic therapeutic nanoplatforms, simultaneously activating tumor-specific oxidative stress amplification and cascaded enhanced Fenton reaction for superior cancer therapy with excellent biosafety.
研究领域:
纳米技术
·
癌症治疗
·
化学生物学
·
材料科学
·
药学
✓ 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）