Programmable Therapeutic Nanodevices with Circular Amplification of H2O2 in the Tumor Microenvironment for Synergistic Cancer Therapy - Details

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Abstract：

Tumor　microenvironment　activated　nanodevices　have　remarkable　superiority　to　enhance　therapeutic　efficacy　and　minimize　side　effects,　but　their　practical　applications　are　dramatically　reduced　by　the　low　abundance　and　heterogeneous　distribution　of　specific　stimuli　at　the　tumor　site.　Herein,　programmable　vesicular　nanodevices　based　on　the　triblock　copolymer　containing　poly(ethylene　glycol)　(PEG)　and　poly(caprolactone)　(PCL)　with　peroxalate　esters　(PO)　as　hydrogen　peroxide-responsive　linkage　(PEG-PO-PCL-PO-PEG),　are　developed　for　co-delivery　of　hypoxia-activated　prodrug　(AQ4N)　and　glucose　oxidase　(GOD).　The　obtained　nanodevices　(PAG)　can　be　activated　by　the　high　level　of　H2O2　in　tumor　microenvironment　to　improve　the　permeability　of　membranes　for　glucose　entrance.　Afterward,　the　oxidation　of　glucose　catalyzed　by　GOD　produces　amplified　H2O2　amounts　which　in　turn　induce　complete　destruction　of　PAG　for　fast　release　of　AQ4N　and　GOD.　Ultimately,　the　PAG　can　exert　programmable　therapeutic　effects　from　the　following　aspects:　1)　starvation　therapy　by　cutting　off　the　energy　supply　from　glucose　through　GOD　catalysis;　2)　oxidative　cytotoxicity　after　H2O2　amplification;　3)　chemotherapy　of　AQ4N　activated　by　the　intensified　tumor　hypoxia　microenvironment　after　oxygen　consumption.　The　stimuli　amplification,　controlled　drug　release,　synergistic　therapy,　and　corresponding　mechanisms　of　PAG　are　demonstrated.　Therefore,　the　presented　work　could　provide　significant　new　insights　for　cancer　treatment.　©　2019　WILEY-VCH　Verlag　GmbH　&　Co.　KGaA,　Weinheim

Keyword：

AQ4N; glucose oxidase; H2O2 circular amplification; H2O2-responsiveness; synergistic cancer therapy

Community：

[ 1 ] [Li, J.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 2 ] [Li, J.]Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China
[ 3 ] [Wei, Z.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 4 ] [Wei, Z.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 5 ] [Wei, Z.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 6 ] [Lin, X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 7 ] [Lin, X.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 8 ] [Lin, X.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 9 ] [Zheng, D.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 10 ] [Zheng, D.]Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China
[ 11 ] [Wu, M.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 12 ] [Wu, M.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 13 ] [Wu, M.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 14 ] [Liu, X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 15 ] [Liu, X.]Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China
[ 16 ] [Liu, X.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 17 ] [Liu, X.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 18 ] [Liu, J.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 19 ] [Liu, J.]Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China
[ 20 ] [Liu, J.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 21 ] [Liu, J.]The Liver Center of Fujian Province, Fujian Medical University, Fuzhou, 350025, China
[ 22 ] [Liu, J.]Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China

Reprint 's Address：

[Wu, M.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical UniversityChina

Email：

wmmj0419@163.com

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Source ：

Advanced Healthcare Materials

ISSN： 2192-2640

Year： 2019

Issue： 10

Volume： 8

7 . 3 6 7

JCR@2019

1 0 . 0 0 0

JCR@2023

ESI HC Threshold：236

JCR Journal Grade：1

CAS Journal Grade：2

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WoS CC Cited Count：

SCOPUS Cited Count：

ESI Highly Cited Papers on the List： 0 Unfold All

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Chinese Cited Count：

30 Days PV： 0

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