PMID- 16303202
OWN - NLM
STAT- MEDLINE
DCOM- 20060227
LR  - 20190217
IS  - 0168-3659 (Print)
IS  - 0168-3659 (Linking)
VI  - 110
IP  - 2
DP  - 2006 Jan 10
TI  - Structural optimization of a "smart" doxorubicin-polypeptide conjugate for 
      thermally targeted delivery to solid tumors.
PG  - 362-369
LID - S0168-3659(05)00535-3 [pii]
LID - 10.1016/j.jconrel.2005.10.006 [doi]
AB  - A thermoresponsive, genetically engineered, elastin-like polypeptide (ELP) 
      containing a C-terminal cysteine residue was synthesized and purified by inverse 
      transition cycling (ITC) and conjugated to doxorubicin (Dox) molecules through 
      four different pH-sensitive, maleimide-activated, hydrazone linkers. The 
      efficiency of Dox activation, conjugation ratios to ELP and biophysical 
      characterization-hydrodynamic radius (Rh) and the temperature transition 
      kinetics-of the ELP-Dox conjugates and pH-mediated release of Dox were quantified 
      in this study. Conjugation ratios of the maleimide-activated Dox to the thiol 
      group of a unique cysteine in the ELP were close to unity. The Rh of the 
      conjugate increased as the linker length between the ELP backbone and Dox was 
      increased. The linker structure and length had little effect on the Tt of the 
      ELP-Dox conjugates, as all conjugates exhibited Tt's that were similar to the 
      native ELP. However, the ELP-Dox conjugates with longer linkers exhibited slower 
      transition kinetics compared to the ELP-Dox conjugates with shorter linkers. The 
      highest release of the ELP-Dox conjugate by cleavage of the hydrazone bond at pH 
      4 was nearly 80% over 72 h and was exhibited by the conjugate with the shortest 
      linker.
FAU - Furgeson, Darin Y
AU  - Furgeson DY
AD  - Department of Biomedical Engineering, Duke University, Durham, North Carolina 
      27708-0281, United States.
FAU - Dreher, Matthew R
AU  - Dreher MR
AD  - Department of Biomedical Engineering, Duke University, Durham, North Carolina 
      27708-0281, United States.
FAU - Chilkoti, Ashutosh
AU  - Chilkoti A
AD  - Department of Biomedical Engineering, Duke University, Durham, North Carolina 
      27708-0281, United States. Electronic address: chilkoti@duke.edu.
LA  - eng
GR  - R01 EB00188-1/EB/NIBIB NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20051121
PL  - Netherlands
TA  - J Control Release
JT  - Journal of controlled release : official journal of the Controlled Release 
      Society
JID - 8607908
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Hydrazones)
RN  - 0 (Maleimides)
RN  - 0 (Peptides)
RN  - 2519R1UGP8 (maleimide)
RN  - 80168379AG (Doxorubicin)
RN  - 9007-58-3 (Elastin)
SB  - IM
MH  - Antibiotics, Antineoplastic/*administration & dosage/*chemistry
MH  - Chemical Phenomena
MH  - Chemistry, Physical
MH  - Chromatography, High Pressure Liquid
MH  - Doxorubicin/*administration & dosage/*chemistry
MH  - *Drug Delivery Systems
MH  - Elastin/chemistry
MH  - Escherichia coli/genetics/metabolism
MH  - Hydrazones/chemistry
MH  - Hydrogen-Ion Concentration
MH  - Light
MH  - Maleimides/chemistry
MH  - Neoplasms/*drug therapy
MH  - Peptides/*administration & dosage/*chemistry
MH  - Protein Engineering
MH  - Scattering, Radiation
MH  - Spectrophotometry, Ultraviolet
EDAT- 2005/11/24 09:00
MHDA- 2006/02/28 09:00
CRDT- 2005/11/24 09:00
PHST- 2005/07/14 00:00 [received]
PHST- 2005/09/28 00:00 [revised]
PHST- 2005/10/06 00:00 [accepted]
PHST- 2005/11/24 09:00 [pubmed]
PHST- 2006/02/28 09:00 [medline]
PHST- 2005/11/24 09:00 [entrez]
AID - S0168-3659(05)00535-3 [pii]
AID - 10.1016/j.jconrel.2005.10.006 [doi]
PST - ppublish
SO  - J Control Release. 2006 Jan 10;110(2):362-369. doi: 
      10.1016/j.jconrel.2005.10.006. Epub 2005 Nov 21.