PMID- 20579075
OWN - NLM
STAT- MEDLINE
DCOM- 20100818
LR  - 20141120
IS  - 1349-7006 (Electronic)
IS  - 1347-9032 (Linking)
VI  - 101
IP  - 8
DP  - 2010 Aug
TI  - In vitro and in vivo evaluation of tumor targeting styrene-maleic acid 
      copolymer-pirarubicin micelles: Survival improvement and inhibition of liver 
      metastases.
PG  - 1866-74
LID - 10.1111/j.1349-7006.2010.01619.x [doi]
AB  - Pirarubicin is a derivative of doxorubicin with improved intracellular uptake and 
      reduced cardiotoxicity. We have prepared a micellar formulation of pirarubicin 
      using styrene-maleic acid copolymer (SMA) of mean molecular weight of 1.2 kDa, 
      which exhibits a mean diameter of 248 nm in solution. Being a macromolecule, 
      SMA-pirarubicin micelles exhibit excellent tumor targeting capacity due to the 
      enhanced permeability and retention (EPR) effect. Here we report the antitumor 
      activity of SMA-pirarubicin micelles on human colon and breast cancer cell lines 
      in vitro, and a murine liver metastasis model in vivo. Metastatic tumor 
      microvasculature, necrosis, apoptosis, proliferation, and survival were also 
      investigated using immunohistochemistry for Ki-67, active caspase-3, and CD34, 
      respectively. Drug cytotoxicity in vitro was assessed using MTT 
      (3-[4,5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide) assay. In 
      vivo, SMA-pirarubicin was administered at 100, 150, or 200 mg/kg (pirarubicin 
      equivalent). Tumor microvasculature was also assessed using scanning electron 
      microscopy. Styrene-maleic acid copolymer (SMA)-pirarubicin micelles were toxic 
      against human colorectal and breast cancer cells in vitro. IC(50) was at or below 
      1 muM, free pirarubicin equivalent. In vivo, SMA-pirarubicin at 100 mg/kg reduced 
      tumor volume by 80% and achieved a survival rate of 93% at 40 days after tumor 
      inoculation. Styrene-maleic acid copolymer (SMA)-pirarubicin micelles 
      demonstrated potent antitumor activity in this liver metastases model, 
      contributing to prolonged survival. Histological examination of tumor nodules 
      showed significant reduction and proliferation of tumor cells (>90%). The present 
      results suggest that investigation of the effect of multiple dosing at later time 
      points to further improve survival is warranted.
FAU - Daruwalla, Jurstine
AU  - Daruwalla J
AD  - Department of Surgery, University of Melbourne, Austin Health, Melbourne, 
      Victoria, Australia.
FAU - Nikfarjam, Mehrdad
AU  - Nikfarjam M
FAU - Greish, Khaled
AU  - Greish K
FAU - Malcontenti-Wilson, Cathy
AU  - Malcontenti-Wilson C
FAU - Muralidharan, Vijayaragavan
AU  - Muralidharan V
FAU - Christophi, Chris
AU  - Christophi C
FAU - Maeda, Hiroshi
AU  - Maeda H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100517
PL  - England
TA  - Cancer Sci
JT  - Cancer science
JID - 101168776
RN  - 0 (Maleates)
RN  - 0 (Micelles)
RN  - 0 (Polystyrenes)
RN  - 25300-64-5 (styrene-maleic acid polymer)
RN  - 80168379AG (Doxorubicin)
RN  - D58G680W0G (pirarubicin)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Caspase 3/physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Doxorubicin/administration & dosage/*analogs & derivatives
MH  - Humans
MH  - Liver Neoplasms, Experimental/*prevention & control/*secondary
MH  - Male
MH  - Maleates/*administration & dosage
MH  - Mice
MH  - Mice, Inbred CBA
MH  - Micelles
MH  - Necrosis
MH  - Neoplasms, Experimental/blood supply/*drug therapy/mortality/pathology
MH  - Polystyrenes/*administration & dosage
EDAT- 2010/06/29 06:00
MHDA- 2010/08/19 06:00
CRDT- 2010/06/29 06:00
PHST- 2010/06/29 06:00 [entrez]
PHST- 2010/06/29 06:00 [pubmed]
PHST- 2010/08/19 06:00 [medline]
AID - CAS1619 [pii]
AID - 10.1111/j.1349-7006.2010.01619.x [doi]
PST - ppublish
SO  - Cancer Sci. 2010 Aug;101(8):1866-74. doi: 10.1111/j.1349-7006.2010.01619.x. Epub 
      2010 May 17.