PMID- 21658763
OWN - NLM
STAT- MEDLINE
DCOM- 20111109
LR  - 20211020
IS  - 1878-5905 (Electronic)
IS  - 0142-9612 (Print)
IS  - 0142-9612 (Linking)
VI  - 32
IP  - 27
DP  - 2011 Sep
TI  - Well-defined, reversible disulfide cross-linked micelles for on-demand paclitaxel 
      delivery.
PG  - 6633-45
LID - 10.1016/j.biomaterials.2011.05.050 [doi]
AB  - To minimize premature release of drugs from their carriers during circulation in 
      the blood stream, we have recently developed reversible disulfide cross-linked 
      micelles (DCMs) that can be triggered to release drug at the tumor site or in 
      cancer cells. We designed and synthesized thiolated linear-dendritic polymers 
      (telodendrimers) by introducing cysteines to the dendritic oligo-lysine backbone 
      of our previously reported telodendrimers comprised of linear polyethylene glycol 
      (PEG) and a dendritic cluster of cholic acids. Reversibly cross-linked micelles 
      were then prepared by the oxidization of thiol groups to disulfide bond in the 
      core of micelles after the self-assembly of thiolated telodendrimers. The DCMs 
      were spherical with a uniform size of 28 nm, and were able to load paclitaxel 
      (PTX) in the core with superior loading capacity up to 35.5% (w/w, drug/micelle). 
      Cross-linking of the micelles within the core reduced their apparent critical 
      micelle concentration and greatly enhanced their stability in non-reductive 
      physiological conditions as well as severe micelle-disrupting conditions. The 
      release of PTX from the DCMs was significantly slower than that from 
      non-cross-linked micelles (NCMs), but can be gradually facilitated by increasing 
      the concentration of reducing agent (glutathione) to an intracellular reductive 
      level. The DCMs demonstrated a longer in vivo blood circulation time, less 
      hemolytic activities, and superior toxicity profiles in nude mice, when compared 
      to NCMs. DCMs were found to be able to preferentially accumulate at the tumor 
      site in nude mice bearing SKOV-3 ovarian cancer xenograft. We also demonstrated 
      that the disulfide cross-linked micellar formulation of PTX (PTX-DCMs) was more 
      efficacious than both free drug and the non-cross-linked formulation of PTX at 
      equivalent doses of PTX in the ovarian cancer xenograft mouse model. The 
      anti-tumor effect of PTX-DCMs can be further enhanced by triggering the release 
      of PTX on-demand by the administration of the FDA approved reducing agent, 
      N-acetylcysteine, after PTX-DCMs have reached the tumor site.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Li, Yuanpei
AU  - Li Y
AD  - Department of Biochemistry & Molecular Medicine, UC Davis Cancer Center, 
      University of California Davis, Sacramento, CA 95817, USA. liyuanpei@gmail.com
FAU - Xiao, Kai
AU  - Xiao K
FAU - Luo, Juntao
AU  - Luo J
FAU - Xiao, Wenwu
AU  - Xiao W
FAU - Lee, Joyce S
AU  - Lee JS
FAU - Gonik, Abby M
AU  - Gonik AM
FAU - Kato, Jason
AU  - Kato J
FAU - Dong, Tiffany A
AU  - Dong TA
FAU - Lam, Kit S
AU  - Lam KS
LA  - eng
GR  - R01 CA140449-01A2/CA/NCI NIH HHS/United States
GR  - R01 CA115483-06/CA/NCI NIH HHS/United States
GR  - R01CA140449/CA/NCI NIH HHS/United States
GR  - R01 CA140449/CA/NCI NIH HHS/United States
GR  - R01CA115483/CA/NCI NIH HHS/United States
GR  - R01 CA115483-05/CA/NCI NIH HHS/United States
GR  - R01 CA115483/CA/NCI NIH HHS/United States
GR  - P30 CA093373/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110611
PL  - Netherlands
TA  - Biomaterials
JT  - Biomaterials
JID - 8100316
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Disulfides)
RN  - 0 (Micelles)
RN  - P88XT4IS4D (Paclitaxel)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Chemical Phenomena/drug effects
MH  - Cross-Linking Reagents/*chemistry
MH  - Disease Models, Animal
MH  - Disulfides/*chemistry/toxicity
MH  - Drug Delivery Systems/*methods
MH  - Female
MH  - Hemolysis/drug effects
MH  - Humans
MH  - Kinetics
MH  - Mice
MH  - Mice, Nude
MH  - *Micelles
MH  - Models, Biological
MH  - Ovarian Neoplasms/drug therapy/pathology
MH  - Paclitaxel/*administration & dosage/pharmacology/therapeutic use
MH  - Particle Size
MH  - Spectroscopy, Near-Infrared
MH  - Tissue Distribution/drug effects
MH  - Xenograft Model Antitumor Assays
PMC - PMC3137548
MID - NIHMS299201
EDAT- 2011/06/11 06:00
MHDA- 2011/11/10 06:00
PMCR- 2012/09/01
CRDT- 2011/06/11 06:00
PHST- 2011/04/29 00:00 [received]
PHST- 2011/05/16 00:00 [accepted]
PHST- 2011/06/11 06:00 [entrez]
PHST- 2011/06/11 06:00 [pubmed]
PHST- 2011/11/10 06:00 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
AID - S0142-9612(11)00582-5 [pii]
AID - 10.1016/j.biomaterials.2011.05.050 [doi]
PST - ppublish
SO  - Biomaterials. 2011 Sep;32(27):6633-45. doi: 10.1016/j.biomaterials.2011.05.050. 
      Epub 2011 Jun 11.