PMID- 24606535
OWN - NLM
STAT- MEDLINE
DCOM- 20141218
LR  - 20181202
IS  - 1543-8392 (Electronic)
IS  - 1543-8384 (Linking)
VI  - 11
IP  - 5
DP  - 2014 May 5
TI  - Charge-conversional PEG-polypeptide polyionic complex nanoparticles from simple 
      blending of a pair of oppositely charged block copolymers as an intelligent 
      vehicle for efficient antitumor drug delivery.
PG  - 1562-74
LID - 10.1021/mp4007387 [doi]
AB  - A tumor-acidity-activated charge-conversional polyionic complex nanoparticle 
      system was developed by simply mixing a pair of oppositely charged block 
      copolymers: anionic methoxy poly(ethylene glycol)-b-poly(l-glutamic 
      acid-co-l-phenylalanine) (mPEG-b-P(Glu-co-Phe)) and cationic methoxy 
      poly(ethy1ene glycol)-b-poly(l-lysine-co-l-phenylalanine) (mPEG-b-P(Lys-co-Phe)). 
      The nanoparticles could stay negatively charged under normal physiological pH 
      value and reverse the surface charge to positive at the tumor extracellular 
      environment. Doxorubicin (DOX) was encapsulated into the nanoparticles fabricated 
      by a self-assembly process, and the DOX-loaded polyionic complex nanoparticles 
      (DOX-NPs) retained the charge-conversional property. In vitro DOX release study 
      demonstrated that DOX release was promoted by the significantly increased acidity 
      in endosomes and lysosomes (pH  approximately  5-6). Cellular uptake studies confirmed that the 
      DOX-NPs could be more effectively internalized by cells at the tumor 
      extracellular pH value. In vitro cytotoxicity assays demonstrated that the 
      polyionic complex nanoparticles had good biocompatibility, and DOX-NPs showed 
      efficient cell proliferation inhibition to HeLa and A549 tumor cells. Maximum 
      tolerated dose (MTD) studies revealed that DOX-NPs had a significantly higher MTD 
      (more than 25 mg of DOX/kg) in mice compared to that for free DOX (5 mg of 
      DOX/kg). Furthermore, DOX-NPs showed superior antitumor activity and reduced side 
      toxicity compared to free DOX in A549 tumor bearing nude mice.
FAU - Lv, Shixian
AU  - Lv S
AD  - Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, 
      Chinese Academy of Sciences , Changchun 130022, P. R. China.
FAU - Song, Wantong
AU  - Song W
FAU - Tang, Zhaohui
AU  - Tang Z
FAU - Li, Mingqiang
AU  - Li M
FAU - Yu, Haiyang
AU  - Yu H
FAU - Hong, Hua
AU  - Hong H
FAU - Chen, Xuesi
AU  - Chen X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140417
PL  - United States
TA  - Mol Pharm
JT  - Molecular pharmaceutics
JID - 101197791
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Peptides)
RN  - 0 (Polymers)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/*chemistry/therapeutic use
MH  - Cell Line, Tumor
MH  - Doxorubicin/administration & dosage/chemistry/therapeutic use
MH  - Drug Delivery Systems/*methods
MH  - HeLa Cells
MH  - Humans
MH  - Lung Neoplasms/drug therapy
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Nanoparticles/*chemistry
MH  - Peptides/*chemistry
MH  - Polyethylene Glycols/*chemistry
MH  - Polymers/*chemistry
MH  - Xenograft Model Antitumor Assays
EDAT- 2014/03/13 06:00
MHDA- 2014/12/19 06:00
CRDT- 2014/03/11 06:00
PHST- 2014/03/11 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2014/12/19 06:00 [medline]
AID - 10.1021/mp4007387 [doi]
PST - ppublish
SO  - Mol Pharm. 2014 May 5;11(5):1562-74. doi: 10.1021/mp4007387. Epub 2014 Apr 17.