PMID- 32450093
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20210617
IS  - 1873-4995 (Electronic)
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 324
DP  - 2020 Aug 10
TI  - Reactive oxygen species and enzyme dual-responsive biocompatible drug delivery 
      system for targeted tumor therapy.
PG  - 330-340
LID - S0168-3659(20)30308-4 [pii]
LID - 10.1016/j.jconrel.2020.05.031 [doi]
AB  - Spurred by newly developed drug delivery systems (DDSs), side effects of cancer 
      chemotherapy could be reduced by using multifunctional nanoplatforms. However, 
      the facile synthesis of effective DDSs remains a challenge. Here, a 
      six-arginine-tailed anti-epidermal growth factor receptor (EGFR) affibody was 
      employed to easily synthesize the highly reactive oxygen species (hROS)- and 
      trypsin-responsive 11-mercaptoundecanoic acid-modified gold nanoclusters (MUA-Au 
      NCs) for tumor-targeted drug delivery. The polyarginine moiety of affibody sealed 
      methotrexate (MTX)-loaded MUA-Au NCs through charge effect, as well as leaving 
      the rest targeting fragment of the affibody to specifically bind tumor 
      overexpressed EGFR. As the shell of MUA-Au NCs-MTX-Affibody (MAMA), polyarginine 
      chains of affibody could be digested by trypsin, helping to release MTX from 
      MAMA. The released MTX accelerated destroying MUA-Au NCs through inducing the 
      generation of hROS. Specifically targeting EGFR-overexpressed tumors, quickly 
      delivering a sufficient amount of drug to the tumor, subsequently increasing the 
      local MTX and hROS levels, and safely eliminating the biocompatible structure 
      from kidney, endowed MAMA greater treatment effectiveness and lower side effect 
      than chemotherapy, especially in pancreatic cancer due to its high trypsin level. 
      This simply fabricated DDS may find applications in high effective cancer 
      therapy, especially for tumors with high trypsin activity.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Zhao, Ning
AU  - Zhao N
AD  - Department of Radiology, Molecular Imaging Program at Stanford, Stanford 
      University, Palo Alto, California 94305, United States. Electronic address: 
      zhaoning@stanford.edu.
FAU - Ding, Bingbing
AU  - Ding B
AD  - Department of Radiology, Molecular Imaging Program at Stanford, Stanford 
      University, Palo Alto, California 94305, United States.
FAU - Zhang, Ying
AU  - Zhang Y
AD  - Institute of Molecular Medicine, College of Life and Health Sciences, 
      Northeastern University, Shenyang 110000, PR China.
FAU - Klockow, Jessica L
AU  - Klockow JL
AD  - Department of Radiology, Molecular Imaging Program at Stanford, Stanford 
      University, Palo Alto, California 94305, United States.
FAU - Lau, Ken
AU  - Lau K
AD  - Department of Radiology, Molecular Imaging Program at Stanford, Stanford 
      University, Palo Alto, California 94305, United States.
FAU - Chin, Frederick T
AU  - Chin FT
AD  - Department of Radiology, Molecular Imaging Program at Stanford, Stanford 
      University, Palo Alto, California 94305, United States.
FAU - Cheng, Zhen
AU  - Cheng Z
AD  - Department of Radiology, Molecular Imaging Program at Stanford, Stanford 
      University, Palo Alto, California 94305, United States. Electronic address: 
      zcheng@stanford.edu.
FAU - Liu, Hongguang
AU  - Liu H
AD  - Institute of Molecular Medicine, College of Life and Health Sciences, 
      Northeastern University, Shenyang 110000, PR China. Electronic address: 
      simonliu@mail.neu.edu.cn.
LA  - eng
GR  - P30 CA124435/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200523
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Reactive Oxygen Species)
RN  - 7440-57-5 (Gold)
RN  - YL5FZ2Y5U1 (Methotrexate)
SB  - IM
MH  - Drug Delivery Systems
MH  - Gold
MH  - Humans
MH  - *Metal Nanoparticles
MH  - Methotrexate
MH  - *Neoplasms/drug therapy
MH  - Reactive Oxygen Species
PMC - PMC8006592
MID - NIHMS1678548
OTO - NOTNLM
OT  - Cancer therapy
OT  - Drug delivery
OT  - Gold nanocluster
OT  - Reactive oxygen species
OT  - Trypsin
COIS- Declaration of Competing Interest The authors declare no competing financial 
      interest.
EDAT- 2020/05/26 06:00
MHDA- 2021/06/22 06:00
PMCR- 2021/03/29
CRDT- 2020/05/26 06:00
PHST- 2020/01/31 00:00 [received]
PHST- 2020/05/06 00:00 [revised]
PHST- 2020/05/20 00:00 [accepted]
PHST- 2020/05/26 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2020/05/26 06:00 [entrez]
PHST- 2021/03/29 00:00 [pmc-release]
AID - S0168-3659(20)30308-4 [pii]
AID - 10.1016/j.jconrel.2020.05.031 [doi]
PST - ppublish
SO  - J Control Release. 2020 Aug 10;324:330-340. doi: 10.1016/j.jconrel.2020.05.031. 
      Epub 2020 May 23.