Nanomaterials
·
2022
·Vol. 12
·期 4
·625
·
IF 5.719
Chao Deng,Xianghai Li,Qianru Jin,Deliang Yi
Enzyme therapy has important implications for the treatment of metabolic disorders and biological detoxification. It remains challenging to prepare enzymatic nanoreactors with high therapeutic efficiency and low emission of cytotoxic reaction intermediates. Here, we propose a novel strategy for the preparation of enzymes-loaded polypeptide microcapsules (EPM) with concentrically encapsulated enzymes to achieve higher cascade reaction rates and minimal emission of cytotoxic intermediates. Mesoporous silica spheres (MSS) are used as a highly porous matrix to efficiently load a therapeutic enzyme (glucose oxidase, GOx), and a layer-by-layer (LbL) assembly strategy is employed to assemble the scavenging enzyme (catalase) and polyelectrolyte multilayers on the MSS surface. After removal of the MSS, a concentrically encapsulated EPM is obtained with the therapeutic enzyme encapsulated inside the capsule, and the scavenging enzyme immobilized in the polypeptide multilayer shell. Performance of the concentrically encapsulated GOx-catalase capsules is investigated for synergistic glucose metabolism disturbance correction and cytotoxic intermediate H2O2clearance. The results show that the EPM can simultaneously achieve 99% H2O2clearance and doubled glucose consumption rate. This strategy can be extended to the preparation of other dual- or multi-enzyme therapeutic nanoreactors, showing great promise in the treatment of metabolic disorders.Keywords:therapeutic nanoreactor;mesoporous silica;enzyme therapy;capsule;metabolic disorder redressing
研究领域:
生物医学工程
·
生物化学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
·
2022
·
IF 14.224
Meng Ding,Wei Zhao,Xu Zhang,Lingjie Song,Shifang Luan
Bacterial biofilm is notorious for causing chronic infections, whose antibiotic treatment is bringing about severe multidrug resistance and environmental contamination. Stimuli-responsive nanocarriers have become encouraging materials to combat biofilm infections with high efficiency and low side effect. Herein, a charge-switchable and pH-responsive nanocomplex is fabricated via a facile aqueous one-pot zeolitic imidazolate framework-8 (ZIF-8) encapsulation of proteinase K (PK) and photosensitizer Rose Bengal (RB), for enzymatic and photodynamic therapies (PDT) against biofilm infections. Once encountering in acidic microenvironment, the surface charge of nanocomplex can switch self-adaptively from negative to positive, hence remarkably facilitating the biofilm penetration of nanocomplex. After acid-induced decomposition of nanocomplex, the released PK degrades biofilm matrix and loosens its structure, promoting diffusion of RB inside the biofilm. Afterwards, upon visible light illumination, the RB generates highly reactive oxygen species (ROS), which can readily and efficiently kill the remained bacteria even in the biofilm core. The charge-assisted penetration makes PK and RB fully functional, resulting in a cooperative effect concerning high biofilm eradication capacity, as testified by biofilm models both in vitro and in vivo . The green synthesis and good therapeutic performance of the nanocomplex manifests its considerable potential as a nontoxic and effective platform for biofilm treatment.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Lunjie Huang,Hongbin Pu,Da-Wen Sun
Nanozyme therapy holds promise for overcoming daunting antimicrobial resistance, but skills to target the microbial microenvironment are lacking. Herein, an isoreticular principle was introduced in nanozyme discovery to directedly evolve a domino biomimetic reaction specific to drug-resistant bacterial biofilm. The isoreticular Ce-UiO-66-X (X = BDC, BDC-CH 3 , BDC-OH, BDC-NH 2 , BDC-NO 2 , ADC, Fum) MOFs exhibited linker-dependent mimicry of hydrolytic apyrase and redox oxidase, and the phosphorous reactants (ATP/ADP/AMP/Pi) produced by the ATP hydrolysis could spontaneously activate redox reaction in Ce-UiO-66-X. Evidenced by the representative Ce-BDC-X (X = –NO 2 , -H, and –NH 2 ) nanozymes, the unique domino reaction of Ce-UiO-66-X could simultaneously deplete ATP molecules and trigger enhanced generation of superoxide radicals at the specific time window in the initial bacterial adhesion stage of methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation. Due to the synergistic nanocatalytic mechanism, possible nanoscale penetration effect, and good biocompatibility, Ce-UiO-66-NO 2 could effectively target and destroy the metabolic microenvironment of MRSA biofilm in vitro and in vivo, reducing the MRSA biofilm viability to as low as 3.64%. This work demonstrates a new prodrug-like enzymodynamic antibacterial therapeutics based on cooperative multienzyme reactivity.
研究领域:
纳米技术
·
生物化学
·
微生物学
·
材料科学
·
治疗学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jianqing Peng,Jia Zhou,Xing Liu,Xiaobo Zhang,Xiang Zhou,Zipeng Gong,Yi Chen,Xiangchun Shen,Yan Chen
Glucose oxidase (GOx)-based enzyme therapeutics are potential alternatives for colorectal cancer (CRC) treatment via glucose consumption and accumulation of hydrogen peroxide (H 2 O 2 ). Given that H 2 O 2 can be eliminated by cytoprotective autophagy, autophagy inhibitors that can interrupt autolysosome-induced H 2 O 2 elimination are promising combination drugs of GOx. Here, we developed a multifunctional biomimetic nanocarrier for effective co-delivery of an autophagy inhibitor-chloroquine phosphate (CQP) and GOx to exert their synergistic effect by irreversibly upregulating intracellular reactive oxygen species (ROS) levels. Poly (D, l -lactide- co -glycolide) (PLGA) nanoparticles (NPs) were used to encapsulate both GOx and CQP using a W/O/W multi-emulsion method. Calcium phosphate (CaP) was used to “fix” CQP to GOx in the internal water phase, where it served as a pH-sensitive unit to facilitate intracellular drug release. Folic acid-modified red blood cell membranes (FR) were used to camouflage the GOx/CQP/CaP encapsulated PLGA NPs (referred to as PLGA/GCC@FR). In an AOM/DSS-induced CRC mouse model, PLGA/GCC@FR exhibited improved antitumor effects, in which the number of tumor nodes were only a quarter of that in the free drug combination group. The enhanced therapeutic effects of PLGA/GCC@FR were attributed to the prolonged tumor retention which was verified by both dynamic in vivo imaging and drug biodistribution . This multifunctional biomimetic nanocarrier facilitated combined enzyme therapeutics by depleting glucose and augmenting intracellular ROS levels in tumor cells, which exerted a synergistic inhibitory effect on tumor growth. Therefore, this study proposed a novel strategy for the enhancement of combined enzyme therapeutics, which provided a promising method for effective CRC treatment.
研究领域:
癌症生物学
·
药学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Ge Li,Yibing Huang,Linlu Zhao,Bo Yang,Jiale Guo,Juntao Hu,Jinli Wang,Hui Wang,Bin Liu,Aiguo Zhang,Fengying Sun,Quan Luo
The development of cell-like nanoreactors with the ability to initiate biocatalytic cascades under special conditions holds tremendous potential for therapeutic applications. Herein, conformationally gated nanoreactors that respond to the acidic microenvironment of infected diabetic wounds were developed by cucur[8]bituril (CB[8])-based supramolecular assembly. The bioinspired nanoreactors exhibit not only self-regulated permeability and selectivity to control internal enzyme activities by substance exchange but also distinct binding specificities toward Gram-positive and Gram-negative bacteria via noncovalent modification with different ligands. The encapsulation of glucose oxidase (GOx), Fe3O4 nanozyme, and l-arginine (l-Arg) into the nanocarriers enables intelligent activation of multienzyme cascade reactions upon glucose (Glu) uptake to produce gluconic acid (GA) and hydrogen peroxide (H2O2), which is further converted into highly toxic hydroxyl radicals (·OH) for selective antibacterial activity. Moreover, acidic H2O2 promotes the oxidization of l-Arg, leading to the release of nitric oxide (NO). Consequently, this nanoreactor provides a multifunctional and synergistic platform for diabetic chronic wound healing by combining enzyme dynamic therapy with NO gas therapy to combat bacterial infections and inflammation under high blood Glu levels.
研究领域:
纳米技术
·
生物医学工程
·
药学
·
伤口愈合
·
酶疗法
·
抗菌剂
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 37
·8546-8557
·
IF 5.344
Qiang Chu,Huimin Zhu,Bin Liu,Guodong Cao,Chao Fang,Yulian Wu,Xiang Li,Gaorong Han
Amino acids are the fundamental building blocks of proteins in tumor cells. The consumption of amino acid can be an effective approach for destroying the tumor cytoskeleton and malfunctioning of the intracellular metabolic balance. Following this concept, herein, amino acid oxidase (AAO) is delivered by hollow Fe3+/tannic acid nanocapsules (HFe–TA) and incorporated within the cancer cell membrane (M) for the first time for synergistic tumor therapy. In this system (M@AAO@HFe–TA), the intracellularly delivered AAO molecules catalyze the oxidative deamination effectively and consume amino acids significantly. The upregulation of intracellular acid and H2O2 concentration facilitates the HFe–TA mediated Fenton reaction and enhances the induction of cytotoxic ˙OH. With the combined effects, considerable in vitro and in vivo tumor inhibition was achieved by M@AAO@Fe–TA due to the activated Bcl-2/Bax/Cyt C/caspase 3 mitochondrial apoptotic pathway. This study offers an alternative therapeutic platform, functioning as a biomimetic cascade nanozyme, to enable synergistic starvation and chemodynamic tumor therapy with high efficacy.
研究领域:
生物医学工程
·
癌症研究
·
酶疗法
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）