PMID- 34119887
OWN - NLM
STAT- MEDLINE
DCOM- 20210826
LR  - 20220531
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Linking)
VI  - 275
DP  - 2021 Aug
TI  - Self-preparation system using glucose oxidase-inspired nitroreductase 
      amplification for cascade-responsive drug release and multidrug resistance 
      reversion.
PG  - 120927
LID - S0142-9612(21)00283-0 [pii]
LID - 10.1016/j.biomaterials.2021.120927 [doi]
AB  - Early antitumor therapy is an important determinant of survival in patients with 
      cancer. Utilization of specific pathological states, such as hypoxia, greatly 
      promotes the development of intelligent drug delivery systems (DDSs) for targeted 
      antitumor therapy. However, a slight decrease in oxygen levels in early-stage 
      tumors is not sufficient to trigger hypoxia-responsive drug release. 
      Nitroreductase (NTR) is overexpressed in bioreductive hypoxic cancers, and its 
      expression level has been verified to be directly related to hypoxic status. 
      Herein, using glucose oxidase (GOx) as an O(2)-consuming agent to exacerbate 
      hypoxia, a cascade strategy of GOx-induced overexpression of NTR and amplified 
      NTR-catalyzed release was proposed for early antitumor therapy. Briefly, 
      NTR-sensitive p-nitrobenzyl chloroformate (PNZ-Cl) was adopted to conjugate with 
      the polysaccharide chitosan (CS) and self-assemble into CS-PNZ-Cl micelles. These 
      polymer micelles possess the dual abilities to specifically immobilize GOx and 
      load mitoxantrone (MIT) to form the NTR-responsive nanocascade reactor 
      GOx/MIT@CS-PNZ-Cl. First, as a "key", tumor hypoxia triggers the initial release 
      of GOx, which serves as the O(2)-consuming agent when catalyzing its reaction 
      with glucose, which is accompanied by H(2)O(2) production. Depleted oxygen levels 
      facilitate the expression of NTR, which in turn amplifies the capacity of the 
      nanocascade reactor to decompose into secondary micelles for enhanced 
      intratumoral permeation. GOx-inspired NTR amplification further elicits MIT 
      release, realizing a synergistic "domino effect" cascade. In addition, 
      upregulated H(2)O(2) has been shown to effectively reverse GSH-mediated MIT 
      resistance, reaching the superior tumor inhibition rate of 93.08%. This GOx-based 
      NTR-responsive nanocascade reactor provides amplification of the bioreductive 
      hypoxic tumor microenvironment for early antitumor therapy.
CI  - Copyright (c) 2021 Elsevier Ltd. All rights reserved.
FAU - Yu, Fangying
AU  - Yu F
AD  - College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, People's Republic of China.
FAU - Shang, Xuwei
AU  - Shang X
AD  - College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, People's Republic of China.
FAU - Zhu, Yun
AU  - Zhu Y
AD  - Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of 
      Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
FAU - Lou, Haiya
AU  - Lou H
AD  - Department of Diagnostic Ultrasound and Echocardiography, Sir Run Run Shaw 
      Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
FAU - Liu, Yupeng
AU  - Liu Y
AD  - College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, People's Republic of China.
FAU - Meng, Tingting
AU  - Meng T
AD  - College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, People's Republic of China.
FAU - Hong, Yun
AU  - Hong Y
AD  - The First Affiliated Hospital, College of Medicine, Zhejiang University, 
      Hangzhou, 310006, China.
FAU - Yuan, Hong
AU  - Yuan H
AD  - College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, People's Republic of China.
FAU - Hu, Fuqiang
AU  - Hu F
AD  - College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, 
      Hangzhou, 310058, People's Republic of China. Electronic address: 
      hufq@zju.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210601
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.1.3.4 (Glucose Oxidase)
RN  - EC 1.7.- (Nitroreductases)
SB  - IM
MH  - Drug Liberation
MH  - Drug Resistance, Multiple
MH  - Drug Resistance, Neoplasm
MH  - *Glucose Oxidase/metabolism
MH  - Humans
MH  - *Hydrogen Peroxide
MH  - Neoplasms/*drug therapy
MH  - Nitroreductases/genetics
OTO - NOTNLM
OT  - Bioreductive hypoxic tumor microenvironment
OT  - Cascade nitroreductase-responsive release
OT  - Glucose oxidase
OT  - Mitoxantrone
EDAT- 2021/06/14 06:00
MHDA- 2021/08/27 06:00
CRDT- 2021/06/13 20:50
PHST- 2020/12/21 00:00 [received]
PHST- 2021/05/10 00:00 [revised]
PHST- 2021/05/25 00:00 [accepted]
PHST- 2021/06/14 06:00 [pubmed]
PHST- 2021/08/27 06:00 [medline]
PHST- 2021/06/13 20:50 [entrez]
AID - S0142-9612(21)00283-0 [pii]
AID - 10.1016/j.biomaterials.2021.120927 [doi]
PST - ppublish
SO  - Biomaterials. 2021 Aug;275:120927. doi: 10.1016/j.biomaterials.2021.120927. Epub 
      2021 Jun 1.