PMID- 32944399
OWN - NLM
STAT- MEDLINE
DCOM- 20211129
LR  - 20211129
IS  - 2095-3941 (Print)
IS  - 2095-3941 (Linking)
VI  - 17
IP  - 3
DP  - 2020 Aug 15
TI  - An ATF(24) peptide-functionalized beta-elemene-nanostructured lipid carrier combined 
      with cisplatin for bladder cancer treatment.
PG  - 676-692
LID - 10.20892/j.issn.2095-3941.2020.0454 [doi]
AB  - Objective: In this study, we aimed to develop an amino-terminal fragment (ATF) 
      peptide-targeted liposome carrying beta-elemene (ATF(24)-PEG-Lipo-beta-E) for targeted 
      delivery into urokinase plasminogen activator receptor-overexpressing bladder 
      cancer cells combined with cisplatin (DDP) for bladder cancer treatment. Methods: 
      The liposomes were prepared by ethanol injection and high-pressure microjet 
      homogenization. The liposomes were characterized, and the drug content, 
      entrapment efficiency, and in vitro release were studied. The targeting 
      efficiency was investigated using confocal microscopy, ultra-fast liquid 
      chromatography, and an orthotopic bladder cancer model. The effects of 
      ATF(24)-PEG-Lipo-beta-E combined with DDP on cell viability and proliferation were 
      evaluated by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, and 
      cell apoptosis and cell cycle analyses. The anticancer effects were evaluated in 
      a KU-19-19 bladder cancer xenograft model. Results: ATF(24)-PEG-Lipo-beta-E had 
      small and uniform sizes ( 79 nm), high drug loading capacity ( 5.24 mg/mL), high 
      entrapment efficiency (98.37 +/- 0.95%), and exhibited sustained drug release 
      behavior. ATF(24)-PEG-Lipo-beta-E had better targeting efficiency and higher 
      cytotoxicity than polyethylene glycol (PEG)ylated beta-elemene liposomes 
      (PEG-Lipo-beta-E). DDP, combined with ATF(24)-PEG-Lipo-beta-E, exerted a synergistic 
      effect on cellular apoptosis and cell arrest at the G2/M phase, and these effects 
      were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 
      pathways. Furthermore, the in vivo antitumor activity showed that the targeted 
      liposomes effectively inhibited the growth of tumors, using the combined 
      strategy. Conclusions: The present study provided an effective strategy for the 
      targeted delivery of beta-elemene (beta-E) to bladder cancer, and a combined strategy 
      for bladder cancer treatment.
CI  - Copyright: (c) 2020, Cancer Biology & Medicine.
FAU - Zhai, Bingtao
AU  - Zhai B
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 
      611137, China.
FAU - Chen, Peng
AU  - Chen P
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Wang, Wengang
AU  - Wang W
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Liu, Shuiping
AU  - Liu S
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Feng, Jiao
AU  - Feng J
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Duan, Ting
AU  - Duan T
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Xiang, Yu
AU  - Xiang Y
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Zhang, Ruonan
AU  - Zhang R
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Zhang, Mingming
AU  - Zhang M
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Han, Xuemeng
AU  - Han X
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Chen, Xiaying
AU  - Chen X
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Li, Qiujie
AU  - Li Q
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Li, Guohua
AU  - Li G
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Liu, Ying
AU  - Liu Y
AD  - Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, 
      Hangzhou 310016, China.
FAU - Huang, Xingxing
AU  - Huang X
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Zhang, Wenzheng
AU  - Zhang W
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Pan, Ting
AU  - Pan T
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Yan, Lili
AU  - Yan L
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Jin, Ting
AU  - Jin T
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Xie, Tian
AU  - Xie T
AUID- ORCID: 0000-0002-6612-0916
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
FAU - Sui, Xinbing
AU  - Sui X
AUID- ORCID: 0000-0001-7330-0467
AD  - Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal 
      University, College of Medicine, Hangzhou Normal University, Hangzhou 310018, 
      China.
AD  - Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province 
      and Engineering Laboratory of Development and Application of Traditional Chinese 
      Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou 310018, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Cancer Biol Med
JT  - Cancer biology & medicine
JID - 101588850
RN  - 0 (Antineoplastic Agents, Phytogenic)
RN  - 0 (Cyclin B1)
RN  - 0 (Liposomes)
RN  - 0 (Sesquiterpenes)
RN  - 0 (beta-elemene)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
RN  - Q20Q21Q62J (Cisplatin)
MH  - Animals
MH  - Antineoplastic Agents, Phytogenic/*pharmacology
MH  - Apoptosis/drug effects
MH  - CDC2 Protein Kinase
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cisplatin/*pharmacology
MH  - Cyclin B1/metabolism
MH  - Female
MH  - G2 Phase Cell Cycle Checkpoints/drug effects
MH  - Humans
MH  - Liposomes/metabolism
MH  - Mice
MH  - Mice, Nude
MH  - Sesquiterpenes/*pharmacology
MH  - Urinary Bladder Neoplasms/*drug therapy/metabolism/pathology
MH  - Xenograft Model Antitumor Assays
PMC - PMC7476079
OTO - NOTNLM
OT  - DDP
OT  - active targeting liposome
OT  - bladder cancer
OT  - uPAR
OT  - beta-elemene
EDAT- 2020/09/19 06:00
MHDA- 2020/09/19 06:01
PMCR- 2020/08/15
CRDT- 2020/09/18 05:51
PHST- 2019/12/29 00:00 [received]
PHST- 2020/06/08 00:00 [accepted]
PHST- 2020/09/18 05:51 [entrez]
PHST- 2020/09/19 06:00 [pubmed]
PHST- 2020/09/19 06:01 [medline]
PHST- 2020/08/15 00:00 [pmc-release]
AID - j.issn.2095-3941.2020.0454 [pii]
AID - 10.20892/j.issn.2095-3941.2020.0454 [doi]
PST - ppublish
SO  - Cancer Biol Med. 2020 Aug 15;17(3):676-692. doi: 
      10.20892/j.issn.2095-3941.2020.0454.