PMID- 32263833
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200408
IS  - 2050-7518 (Electronic)
IS  - 2050-750X (Linking)
VI  - 5
IP  - 4
DP  - 2017 Jan 28
TI  - A multi-stimuli responsive nanoparticulate SN38 prodrug for cancer chemotherapy.
PG  - 661-670
LID - 10.1039/c6tb02262f [doi]
AB  - Modification of drug delivery systems (DDSs) with stimuli-responsive elements 
      could significantly increase the tumor-specific delivery of anticancer drugs. 
      Herein we synthesized a novel multiple stimuli-responsive SN38 prodrug, named 
      PEG-S-S-SN38, by conjugating PEG (M(W): 2000) and SN38 with disulfide bonds and 
      carbonic ester linkages as linkers for efficient delivery of SN38. The 
      amphiphilic PEG-S-S-SN38, with a high SN38 loading content, could self-assemble 
      into nanoparticles (NPs) with a stable diameter of  approximately 73 nm. PEG-S-S-SN38 NPs 
      release SN38 very slowly at physiological pH, while they quickly release SN38 in 
      the presence of GSH, esterase and H(2)O(2), all of which are abundant in the 
      cytoplasm of cancer cells. PEG-S-S-SN38 NPs could be quickly internalized into 
      tumor cells, achieve vesicular escape and nuclear localization, and exhibit 
      remarkable in vitro anticancer activity similar to SN38. Encouragingly, 
      PEG-S-S-SN38 NPs exhibit the same effects on cell cycle regulations as SN38 in 
      vitro. Most importantly, the inhibition rate of tumor growth induced by 
      PEG-S-S-SN38 NPs in a xenograft tumor model reached 72.49% +/- 6.26%, which was 
      nearly double that of the corresponding clinical drug CPT-11 (38.64% +/- 13.04%) at 
      a dosage equivalent to 10 mg kg(-1) SN38. Our data suggest that the multi-stimuli 
      responsiveness of PEG-S-S-SN38 NPs remarkably enhances their therapeutic activity 
      against heterogeneous or mixed cell population in tumors, making this new DDS a 
      promising alternative to CPT-11 for cancer treatment.
FAU - Liu, Xun
AU  - Liu X
AD  - College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 
      310027, China.
FAU - Huang, Qian
AU  - Huang Q
FAU - Yang, Caixia
AU  - Yang C
FAU - Zhang, Qianzhi
AU  - Zhang Q
FAU - Chen, Wan
AU  - Chen W
FAU - Shen, Youqing
AU  - Shen Y
FAU - Sui, Meihua
AU  - Sui M
LA  - eng
PT  - Journal Article
DEP - 20161130
PL  - England
TA  - J Mater Chem B
JT  - Journal of materials chemistry. B
JID - 101598493
SB  - IM
EDAT- 2017/01/28 00:00
MHDA- 2017/01/28 00:01
CRDT- 2020/04/09 06:00
PHST- 2020/04/09 06:00 [entrez]
PHST- 2017/01/28 00:00 [pubmed]
PHST- 2017/01/28 00:01 [medline]
AID - 10.1039/c6tb02262f [doi]
PST - ppublish
SO  - J Mater Chem B. 2017 Jan 28;5(4):661-670. doi: 10.1039/c6tb02262f. Epub 2016 Nov 
      30.