PMID- 19440379
OWN - NLM
STAT- MEDLINE
DCOM- 20090806
LR  - 20211020
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 5
DP  - 2009
TI  - Adenovirus dodecahedron, as a drug delivery vector.
PG  - e5569
LID - 10.1371/journal.pone.0005569 [doi]
LID - e5569
AB  - BACKGROUND: Bleomycin (BLM) is an anticancer antibiotic used in many cancer 
      regimens. Its utility is limited by systemic toxicity and dose-dependent 
      pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 
      50% of the total patient population, out of which 3% will die. We propose to 
      improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus 
      (Ad) dodecahedron base (DB) is a particulate vector composed of 12 copies of a 
      pentameric viral protein responsible for virus penetration. The vector 
      efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has 
      a propensity to concentrate around the nucleus; up to 300000 particles can be 
      observed in one cell in vitro. PRINCIPAL FINDINGS: Dodecahedron (Dd) structure is 
      preserved at up to about 50 degrees C at pH 7-8 and during dialysis, freezing and 
      drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as 
      during lyophilization in the presence of cryoprotectants. The vector is also 
      stable in human serum for 2 h at 37 degrees C. We prepared a Dd-BLM conjugate 
      which upon penetration induced death of transformed cells. Similarly to free 
      bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic 
      concentration of BLM delivered with Dd was 100 times lower than that of free 
      bleomycin. CONCLUSIONS/SIGNIFICANCE: Stability studies show that Dds can be 
      conveniently stored and transported, and can potentially be used for therapeutic 
      purposes under various climates. Successful BLM delivery by Ad Dds demonstrates 
      that the use of virus like particle (VLP) results in significantly improved drug 
      bioavailability. These experiments open new vistas for delivery of non-permeant 
      labile drugs.
FAU - Zochowska, Monika
AU  - Zochowska M
AD  - Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, 
      Poland.
FAU - Paca, Agnieszka
AU  - Paca A
FAU - Schoehn, Guy
AU  - Schoehn G
FAU - Andrieu, Jean-Pierre
AU  - Andrieu JP
FAU - Chroboczek, Jadwiga
AU  - Chroboczek J
FAU - Dublet, Bernard
AU  - Dublet B
FAU - Szolajska, Ewa
AU  - Szolajska E
LA  - eng
GR  - 2P04B02329/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20090515
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Recombinant Proteins)
RN  - 0 (Viral Proteins)
RN  - 11056-06-7 (Bleomycin)
RN  - 5DY91Y7601 (bleomycetin)
SB  - IM
MH  - Adenoviridae/chemistry/genetics/*metabolism
MH  - Bleomycin/analogs & derivatives/chemistry
MH  - Drug Delivery Systems/*methods
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Flow Cytometry
MH  - Genetic Vectors/chemistry/genetics/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Microscopy, Atomic Force
MH  - Microscopy, Confocal
MH  - Microscopy, Fluorescence
MH  - Recombinant Proteins/chemistry/genetics/metabolism
MH  - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
MH  - Viral Proteins/chemistry/genetics/*metabolism
PMC - PMC2679213
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/05/15 09:00
MHDA- 2009/08/07 09:00
PMCR- 2009/05/15
CRDT- 2009/05/15 09:00
PHST- 2008/12/19 00:00 [received]
PHST- 2009/04/20 00:00 [accepted]
PHST- 2009/05/15 09:00 [entrez]
PHST- 2009/05/15 09:00 [pubmed]
PHST- 2009/08/07 09:00 [medline]
PHST- 2009/05/15 00:00 [pmc-release]
AID - 08-PONE-RA-07852R1 [pii]
AID - 10.1371/journal.pone.0005569 [doi]
PST - ppublish
SO  - PLoS One. 2009;4(5):e5569. doi: 10.1371/journal.pone.0005569. Epub 2009 May 15.