PMID- 26153904
OWN - NLM
STAT- MEDLINE
DCOM- 20160506
LR  - 20150810
IS  - 1526-4602 (Electronic)
IS  - 1525-7797 (Linking)
VI  - 16
IP  - 8
DP  - 2015 Aug 10
TI  - Thermoresponsive Polymer Micelles as Potential Nanosized Cancerostatics.
PG  - 2493-505
LID - 10.1021/acs.biomac.5b00764 [doi]
AB  - An effective chemotherapy for neoplastic diseases requires the use of drugs that 
      can reach the site of action at a therapeutically efficacious concentration and 
      maintain it at a constant level over a sufficient period of time with minimal 
      side effects. Currently, conjugates of high-molecular-weight hydrophilic polymers 
      or biocompatible nanoparticles with stimuli-releasable anticancer drugs are 
      considered to be some of the most promising systems capable of fulfilling these 
      criteria. In this work, conjugates of thermoresponsive diblock copolymers with 
      the covalently bound cancerostatic drug pirarubicin (PIR) were synthesized as a 
      reversible micelle-forming drug delivery system combining the benefits of the 
      above-mentioned carriers. The diblock copolymer carriers were composed of 
      hydrophilic poly[N-(2-hydroxypropyl)methacrylamide]-based block containing a 
      small amount ( approximately  5 mol %) of comonomer units with reactive hydrazide groups and a 
      thermoresponsive poly[2-(2-methoxyethoxy)ethyl methacrylate] block. PIR was 
      attached to the hydrophilic block of the copolymer through the pH-sensitive 
      hydrazone bond designed to be stable in the bloodstream at pH 7.4 but to be 
      degraded in an intratumoral/intracellular environment at pH 5-6. The 
      temperature-induced conformation change of the thermoresponsive block 
      (coil-globule transition), followed by self-assembly of the copolymer into a 
      micellar structure, was controlled by the thermoresponsive block length and PIR 
      content. The cytotoxicity and intracellular transport of the conjugates as well 
      as the release of PIR from the conjugates inside the cells, followed by its 
      accumulation in the cell nuclei, were evaluated in vitro using human colon 
      adenocarcinoma (DLD-1) cell lines. It was demonstrated that the studied 
      conjugates have a great potential to become efficacious in vivo pharmaceuticals.
FAU - Laga, Richard
AU  - Laga R
AD  - Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 
      v.v.i., Department of Biomedical Polymers, Heyrovsky square 2, 162 06 Prague, 
      Czech Republic.
FAU - Janouskova, Olga
AU  - Janouskova O
AD  - Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 
      v.v.i., Department of Biomedical Polymers, Heyrovsky square 2, 162 06 Prague, 
      Czech Republic.
FAU - Ulbrich, Karel
AU  - Ulbrich K
AD  - Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 
      v.v.i., Department of Biomedical Polymers, Heyrovsky square 2, 162 06 Prague, 
      Czech Republic.
FAU - Pola, Robert
AU  - Pola R
AD  - Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 
      v.v.i., Department of Biomedical Polymers, Heyrovsky square 2, 162 06 Prague, 
      Czech Republic.
FAU - Blazkova, Jana
AU  - Blazkova J
AD  - Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 
      v.v.i., Department of Biomedical Polymers, Heyrovsky square 2, 162 06 Prague, 
      Czech Republic.
FAU - Filippov, Sergey K
AU  - Filippov SK
AD  - Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 
      v.v.i., Department of Biomedical Polymers, Heyrovsky square 2, 162 06 Prague, 
      Czech Republic.
FAU - Etrych, Tomas
AU  - Etrych T
AD  - Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 
      v.v.i., Department of Biomedical Polymers, Heyrovsky square 2, 162 06 Prague, 
      Czech Republic.
FAU - Pechar, Michal
AU  - Pechar M
AD  - Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, 
      v.v.i., Department of Biomedical Polymers, Heyrovsky square 2, 162 06 Prague, 
      Czech Republic.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150716
PL  - United States
TA  - Biomacromolecules
JT  - Biomacromolecules
JID - 100892849
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Micelles)
RN  - 0 (Polymers)
RN  - 80168379AG (Doxorubicin)
RN  - D58G680W0G (pirarubicin)
SB  - IM
MH  - Antineoplastic Agents/*administration & dosage/chemistry
MH  - Cell Line, Tumor
MH  - Doxorubicin/administration & dosage/*analogs & derivatives/chemistry
MH  - *Drug Delivery Systems
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Hydrophobic and Hydrophilic Interactions
MH  - Micelles
MH  - Nanoparticles/*administration & dosage/chemistry
MH  - Neoplasms/*drug therapy
MH  - Polymers/administration & dosage/chemistry
EDAT- 2015/07/15 06:00
MHDA- 2016/05/07 06:00
CRDT- 2015/07/09 06:00
PHST- 2015/07/09 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2016/05/07 06:00 [medline]
AID - 10.1021/acs.biomac.5b00764 [doi]
PST - ppublish
SO  - Biomacromolecules. 2015 Aug 10;16(8):2493-505. doi: 10.1021/acs.biomac.5b00764. 
      Epub 2015 Jul 16.