PMID- 33961957
OWN - NLM
STAT- MEDLINE
DCOM- 20210617
LR  - 20210617
IS  - 1873-3476 (Electronic)
IS  - 0378-5173 (Linking)
VI  - 603
DP  - 2021 Jun 15
TI  - Reduction-responsive dehydroepiandrosterone prodrug nanoparticles loaded with 
      camptothecin for cancer therapy by enhancing oxidation therapy and cell 
      replication inhibition.
PG  - 120671
LID - S0378-5173(21)00476-2 [pii]
LID - 10.1016/j.ijpharm.2021.120671 [doi]
AB  - The pentose phosphate pathway (PPP) plays a critical role by providing 
      ribulose-5-phosphate (Ru5P) and NADPH for nucleotide synthesis and reduction 
      energy, respectively. Accordingly, blocking the PPP process may be an effective 
      strategy for enhancing oxidation therapy and inhibiting cell replication. Here, 
      we designed a novel reduction-responsive PEGylated prodrug and constructed 
      nanoparticles PsD@CPT to simultaneously deliver a PPP blocker, 
      dehydroepiandrosterone (DHEA), and chemotherapeutic camptothecin (CPT) to 
      integrate amplification of oxidation therapy and enhance cell replication 
      inhibition. Following cellular uptake, DHEA and CPT were released from PsD@CPT in 
      the presence of high glutathione (GSH) levels. As expected, DHEA-mediated 
      reduction level decreases and CPT-induced oxidation level increases 
      synergistically, breaking the redox balance to aggravate cancer oxidative stress. 
      In addition, suppressing nucleotide synthesis by DHEA through the reduction of 
      Ru5P and blocking DNA replication by CPT further motivates a synergistic 
      inhibition effect on tumor cell proliferation. The results showed that PsD@CPT 
      featuring multimodal treatment has satisfactory antitumor activity both in vitro 
      and in vivo. This study provides a new tumor treatment strategy, which combines 
      the amplification of oxidative stress and enhancement of inhibition of cell 
      proliferation based on inhibition of the PPP process.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Xu, Congjun
AU  - Xu C
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Yang, Haolan
AU  - Yang H
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Xiao, Zhanghong
AU  - Xiao Z
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Zhang, Tao
AU  - Zhang T
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Guan, Zilin
AU  - Guan Z
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Chen, Jie
AU  - Chen J
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Lai, Hualu
AU  - Lai H
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Xu, Xiaoyu
AU  - Xu X
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Huang, Yanjuan
AU  - Huang Y
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Huang, Zeqian
AU  - Huang Z
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China.
FAU - Zhao, Chunshun
AU  - Zhao C
AD  - School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, 
      People's Republic of China. Electronic address: zhaocs@mail.sysu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210505
PL  - Netherlands
TA  - Int J Pharm
JT  - International journal of pharmaceutics
JID - 7804127
RN  - 0 (Prodrugs)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - XT3Z54Z28A (Camptothecin)
SB  - IM
MH  - Camptothecin
MH  - Cell Line, Tumor
MH  - DNA Replication
MH  - Dehydroepiandrosterone/therapeutic use
MH  - Drug Delivery Systems
MH  - Humans
MH  - *Nanoparticles
MH  - *Neoplasms/drug therapy
MH  - Oxidation-Reduction
MH  - *Prodrugs/therapeutic use
OTO - NOTNLM
OT  - Cell cycle arrest
OT  - GSH-responsive
OT  - Oxidation therapy
OT  - PEGylated prodrug
OT  - Pentose phosphate pathway
EDAT- 2021/05/08 06:00
MHDA- 2021/06/22 06:00
CRDT- 2021/05/07 20:21
PHST- 2021/01/10 00:00 [received]
PHST- 2021/04/18 00:00 [revised]
PHST- 2021/05/01 00:00 [accepted]
PHST- 2021/05/08 06:00 [pubmed]
PHST- 2021/06/22 06:00 [medline]
PHST- 2021/05/07 20:21 [entrez]
AID - S0378-5173(21)00476-2 [pii]
AID - 10.1016/j.ijpharm.2021.120671 [doi]
PST - ppublish
SO  - Int J Pharm. 2021 Jun 15;603:120671. doi: 10.1016/j.ijpharm.2021.120671. Epub 
      2021 May 5.