Advanced Science
·
2024
·
IF 14.3
Xiao-Lin Hou,Bin Zhang,Kai Cheng,Fang Zhang,Xiao-Ting Xie,Wei Chen,Lin-Fang Tan,Jin-Xuan Fan,Bo Liu,Qiu-Ran Xu
Customizable and number-tunable enzyme delivery nanocarriers will be useful in tumor therapy. Herein, a phage vehicle, T4-Lox-DNA-Fe (TLDF), which adeptly modulates enzyme numbers using phage display technology to remodel the tumor microenvironment (TME) is presented. Regarding the demand for lactic acid in tumors, each phage is engineered to display 720 lactate oxidase (Lox), contributing to the depletion of lactic acid to restructure the tumor's energy metabolism. The phage vehicle incorporated dextran iron (Fe) with Fenton reaction capabilities. H 2 O 2 is generated through the Lox catalytic reaction, amplifying the H 2 O 2 supply for dextran iron-based chemodynamic therapy (CDT). Drawing inspiration from the erythropoietin (EPO) biosynthetic process, an EPO enhancer is constructed to impart the EPO-Keap1 plasmid (DNA) with tumor hypoxia-activated functionality, disrupting the redox homeostasis of the TME. Lox consumes local oxygen, and positive feedback between the Lox and the plasmid promotes the expression of kelch ECH Associated Protein 1 (Keap1). Consequently, the downregulation of the antioxidant transcription factor Nrf2, in synergy with CDT, amplifies the oxidative killing effect, leading to tumor suppression of up to 78%. This study seamlessly integrates adaptable T4 phage vehicles with bio-intelligent plasmids, presenting a promising approach for tumor therapy.
研究领域:
生物医学工程
·
癌症治疗
·
分子生物学
·
纳米技术
·
酶学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2020
·Vol. 8
·期 28
·6139-6147
·
IF 5.344
Fan Wang,Jian Yang,Yongsheng Li,Qixin Zhuang,Jinlou Gu
Enzyme-activated prodrug therapy (EAPT) is an effective cancer treatment strategy able to transport non-toxic prodrugs and subsequently convert them into drugs at specific times and locations. However, due to the limitation of easy biodegradability and the membrane-impermeable characteristic of exogenous enzymes, there is a need to exploit suitable carriers for the effective protection and simultaneous delivery of activating enzymes into cancer cells. Herein, hierarchically porous MOFs were employed for the loading of enzyme and prodrug in a single nanocarrier thanks to their different cavity sizes. The simple loading process allows entrapping of horseradish peroxidase (HRP) and a monocarboxyl-containing indole-3-acetic acid (IAA) prodrug with high loading capacities in different spaces, which keeps the catalytic activity of the enzyme perfectly intact and avoids the premature activation of the prodrug. The encapsulated HRP and IAA exhibit sustained and synchronized release behaviors. Compared to the native HRP enzyme, the current MOF nanocarriers not only facilitate enzyme delivery into cellular lysosomes and subsequent endosomal escape, but also effectively release enzyme and prodrug in the intracellular environment within 48 h. Eventually, HRP and IAA loaded MOF nanocarriers cause significant cell death with a low IC50 of 4.2 mg L−1, while the IAA prodrug alone is non-toxic even at high concentrations. Thus, hierarchically porous MOFs might offer a promising platform for EAPT with a highly consistent spatiotemporal distribution of enzymes and prodrugs in target tissues.
研究领域:
药学
·
纳米技术
·
癌症治疗
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CATALYSIS
·
2019
·
IF 7.723
Liteng Li,Kaijing Liu,Hanli Xing,Xiaofang Li,Qiangguo Zhang,Dandan Han,Hongyan He,Hongyuan Yan,Baokun Tang
Biocompatible and magnetic polymers of poly(vinyl pyrrolidone deep eutectic solvent, VP DES) were investigated to determine whether they could efficiently adsorb L-asparaginase, which is an important enzyme inhibiting the growth of certain tumor cells. A series of poly(VP DES)s were successfully obtained, and that based on VP–malonic acid (VP/MA molar ratio of 1:1) was found to be the best for L-asparaginase adsorption. In addition, L-asparaginase was easily separated with biocompatible poly(VP-MA DES) from Escherichia coli extracts under a magnetic field with a high specific activity toward the hydrolysis of L-asparagine, as determined by the Nessler reaction method. Based on this work, poly(VP-MA DES)s seem ideal carriers via adsorption for the delivery of specific enzyme for the biocatalysis.
研究领域:
材料科学
·
生物化学
·
生物技术
·
药学
✓ 已验证
产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Jingyi Zheng,Rong Zhou,Zhengyu Jin,Tao Zhang,Ming Miao
In response to the challenge of lysozyme (LZM) inactivation in the acidic environment of gastric juice, a pH-responsive gel delivery system based on glucan dendrimer (PG) was developed to achieve targeted intestinal delivery and enhance its bioavailability. Initially, PG was carboxymethylated. Then, a three-dimensional glycosidic bond entanglement network was constructed through enzymatic assembly to prepare the CMPG gel carrier. The structural characteristics of this carrier were characterized using various techniques, such as SEM, FTIR, XRD, and rheological analysis. Additionally, enzymatic hydrolysis experiments were carried out to elucidate the digestion characteristics of PG (or CMPG)-Gel. Subsequently, an in vitro simulated digestion model was employed to evaluate both the release behavior and activity retention rate of LZM under conditions mimicking gastric juice (pH 1.2) and intestinal fluid (pH 7.4). Within two hours in an intestinal environment, the release rate was reached up to 87.51 %, while the structural integrity of LZM was ensured to remain intact. This study represented a novel approach in which PG was utilized as a gel carrier through dual modifications involving carboxymethylation and enzymatic assembly for the first time. Targeted drug release was successfully achieved by leveraging pH responsiveness.
研究领域:
药物递送
·
生物材料
·
药剂学
·
高分子化学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）