A biomimetic nanocarrier facilitates glucose consumption and reactive oxide species accumulation in enzyme therapy for colorectal cancer
Copyright © 2024 Elsevier B.V. All rights reserved..
Glucose oxidase (GOx)-based enzyme therapeutics are potential alternatives for colorectal cancer (CRC) treatment via glucose consumption and accumulation of hydrogen peroxide (H2O2). Given that H2O2 can be eliminated by cytoprotective autophagy, autophagy inhibitors that can interrupt autolysosome-induced H2O2 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/GCCFR). 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:367 |
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| Enthalten in: |
Journal of controlled release : official journal of the Controlled Release Society - 367(2024) vom: 20. März, Seite 76-92 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Peng, Jianqing [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 25.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jconrel.2024.01.041 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM367529068 |
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| 520 | |a Glucose oxidase (GOx)-based enzyme therapeutics are potential alternatives for colorectal cancer (CRC) treatment via glucose consumption and accumulation of hydrogen peroxide (H2O2). Given that H2O2 can be eliminated by cytoprotective autophagy, autophagy inhibitors that can interrupt autolysosome-induced H2O2 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/GCCFR). 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Biomimetic nanoparticles | |
| 650 | 4 | |a Chloroquine phosphate | |
| 650 | 4 | |a Colorectal cancer | |
| 650 | 4 | |a Enzyme therapy | |
| 650 | 4 | |a Glucose oxidase | |
| 650 | 7 | |a Oxides |2 NLM | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 650 | 7 | |a Hydrogen Peroxide |2 NLM | |
| 650 | 7 | |a BBX060AN9V |2 NLM | |
| 650 | 7 | |a Reactive Oxygen Species |2 NLM | |
| 650 | 7 | |a Polylactic Acid-Polyglycolic Acid Copolymer |2 NLM | |
| 650 | 7 | |a 1SIA8062RS |2 NLM | |
| 650 | 7 | |a Glucose Oxidase |2 NLM | |
| 650 | 7 | |a EC 1.1.3.4 |2 NLM | |
| 700 | 1 | |a Zhou, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaobo |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Xiang |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Zipeng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Shen, Xiangchun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yan |e verfasserin |4 aut | |
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