PMID- 20452423
OWN - NLM
STAT- MEDLINE
DCOM- 20101207
LR  - 20181201
IS  - 1873-3441 (Electronic)
IS  - 0939-6411 (Linking)
VI  - 76
IP  - 1
DP  - 2010 Sep
TI  - Secondary cytotoxicity mediated by alveolar macrophages: a contribution to the 
      total efficacy of nanoparticles in lung cancer therapy?
PG  - 112-9
LID - 10.1016/j.ejpb.2010.05.002 [doi]
AB  - Local treatment of lung cancer using inhalable nanoparticles (NPs) is an emerging 
      and promising treatment option. The aim of this study was to investigate the 
      activation of alveolar macrophages by poly (isobutyl cyanoacrylate) (BIPCA) NPs 
      and the consequences of this activation on H460 lung cancer cells. A 
      methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to determine the 
      primary cytotoxicity, that is, the immediate and direct cytotoxicity of 
      doxorubicin (DOX)-loaded NPs on both cell lines. Macrophages were then treated 
      using EC(50) concentrations of different treatments and co-cultured in a 
      two-compartment system with H460 lung cancer cells. These treatments included DOX 
      solution, blank NPs, and DOX-loaded NPs. The results showed that alveolar 
      macrophages exposed to blank or DOX-loaded NPs showed cytotoxicity against cancer 
      cells after 8 and 24h; this behavior was not expressed by naive macrophages or 
      macrophages treated with DOX solution. Sample analysis indicated that macrophages 
      have the ability to release back fragments of NPs that were previously 
      phagocytized. Further investigations showed that NPs can induce an increase in 
      the excretion of Th1 cytokines namely, monocytes chemoattractant protein-1 
      (MCP-1), macrophages inflammatory protein (MIP-1), tumor necrosis factor alpha 
      (TNF-alpha), and interferon gamma (IFN-gamma). The Th1 cytokines released by the 
      alveolar macrophages might explain the significant secondary cytotoxicity effect 
      on H460 cancer cells. Secondary cytotoxicity mediated by macrophages might 
      compliment the direct cytotoxic effect that NPs have on cancer cells.
CI  - 2010 Elsevier B.V. All rights reserved.
FAU - Al-Hallak, Kamal M H D
AU  - Al-Hallak KM
AD  - Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Alberta, 
      Canada.
FAU - Azarmi, Shirzad
AU  - Azarmi S
FAU - Anwar-Mohamed, Anwar
AU  - Anwar-Mohamed A
FAU - Roa, Wilson H
AU  - Roa WH
FAU - Lobenberg, Raimar
AU  - Lobenberg R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100507
PL  - Netherlands
TA  - Eur J Pharm Biopharm
JT  - European journal of pharmaceutics and biopharmaceutics : official journal of 
      Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
JID - 9109778
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cyanoacrylates)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 80168379AG (Doxorubicin)
RN  - 82115-62-6 (Interferon-gamma)
RN  - F8CEP82QNP (Enbucrilate)
SB  - IM
MH  - Administration, Inhalation
MH  - Animals
MH  - Antineoplastic Agents/administration & dosage/chemistry/*pharmacology
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/metabolism
MH  - Coculture Techniques
MH  - Cyanoacrylates/administration & dosage/chemistry/*pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Doxorubicin/administration & dosage/chemistry/*pharmacology
MH  - Enbucrilate
MH  - Humans
MH  - Inhibitory Concentration 50
MH  - Interferon-gamma/metabolism
MH  - Lung Neoplasms/*pathology
MH  - Macrophage Inflammatory Proteins/metabolism
MH  - Macrophages, Alveolar/*drug effects/immunology
MH  - Mice
MH  - *Nanoparticles
MH  - Phagocytosis
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2010/05/11 06:00
MHDA- 2010/12/14 06:00
CRDT- 2010/05/11 06:00
PHST- 2010/01/05 00:00 [received]
PHST- 2010/05/04 00:00 [revised]
PHST- 2010/05/04 00:00 [accepted]
PHST- 2010/05/11 06:00 [entrez]
PHST- 2010/05/11 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
AID - S0939-6411(10)00138-4 [pii]
AID - 10.1016/j.ejpb.2010.05.002 [doi]
PST - ppublish
SO  - Eur J Pharm Biopharm. 2010 Sep;76(1):112-9. doi: 10.1016/j.ejpb.2010.05.002. Epub 
      2010 May 7.