PMID- 30023528
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2470-1343 (Print)
IS  - 2470-1343 (Electronic)
IS  - 2470-1343 (Linking)
VI  - 2
IP  - 10
DP  - 2017 Oct 31
TI  - Photoresponsive Block Copolymer Prodrug Nanoparticles as Delivery Vehicle for 
      Single and Dual Anticancer Drugs.
PG  - 6677-6690
LID - 10.1021/acsomega.7b00911 [doi]
AB  - In recent decades, drug delivery systems (DDSs) based on polymer nanoparticles 
      have been explored due to their potential to deliver drugs with poor water 
      solubility. Some of the limitations of nanoparticle-based DDSs can be overcome by 
      developing an appropriate polymer prodrug. In this work, 
      poly(NIPA)-b-poly(HMNPPA)-b-poly(PEGMA-stat-BA) was synthesized using reversible 
      addition fragmentation chain transfer polymerization and Chlorambucil (Cbl), an 
      anticancer drug, was conjugated to the copolymer via 
      3-(3-(hydroxymethyl)-4-nitrophenoxy)propyl acrylate (HMNPPA) units to prepare the 
      prodrug. A few biotin acrylate (BA) units were also incorporated to bring 
      potential targeting capability to the prodrug in the copolymer. This polymer 
      prodrug formed spherical micellar nanoparticles in physiological conditions, 
      which were characterized by dynamic light scattering and transmission electron 
      microscopy measurements. The very low critical aggregation concentration (cac) 
      (0.011 mg/mL) of the prodrug, as measured from Nile Red fluorescence, makes it 
      stable against dilution. The polymer prodrug was shown to release Cbl on 
      photoirradiation by soft UV (lambda >/= 365 nm) and laser (lambda = 405 nm) light. The 
      prodrug micellar nanoparticles were capable of encapsulating a second drug 
      (doxorubicin, DOX) in their hydrophobic core. On photoirradiation with UV and 
      laser light of the DOX-loaded nanoparticles, both Cbl and DOX were released. 
      Light-induced breaking of photolabile ester bond resulted in the release of Cbl 
      and caused disruption of the nanoparticles facilitating release of DOX. 
      3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay confirmed the 
      nontoxicity of the polymers and effectiveness of the dual drug-loaded micellar 
      nanoparticles toward cancer cells. Confocal microscopy results showed a better 
      cellular internalization capability of the DOX-loaded nanoparticles in cancer 
      cells, possibly due to the presence of cancer cell targeting biotin molecules in 
      the polymer. This new photoresponsive potentially biocompatible and cancer 
      cell-targeted polymer prodrug may be useful for delivery of single and/or 
      multiple hydrophobic drugs.
FAU - Biswas, Gargi
AU  - Biswas G
AD  - Department of Chemistry and School of Medical Science and Technology, Indian 
      Institute of Technology, Kharagpur, West Bengal 721302, India.
FAU - Jena, Bikash Chandra
AU  - Jena BC
AD  - Department of Chemistry and School of Medical Science and Technology, Indian 
      Institute of Technology, Kharagpur, West Bengal 721302, India.
FAU - Maiti, Saikat
AU  - Maiti S
AD  - Department of Chemistry and School of Medical Science and Technology, Indian 
      Institute of Technology, Kharagpur, West Bengal 721302, India.
FAU - Samanta, Pousali
AU  - Samanta P
AD  - Department of Chemistry and School of Medical Science and Technology, Indian 
      Institute of Technology, Kharagpur, West Bengal 721302, India.
FAU - Mandal, Mahitosh
AU  - Mandal M
AD  - Department of Chemistry and School of Medical Science and Technology, Indian 
      Institute of Technology, Kharagpur, West Bengal 721302, India.
FAU - Dhara, Dibakar
AU  - Dhara D
AD  - Department of Chemistry and School of Medical Science and Technology, Indian 
      Institute of Technology, Kharagpur, West Bengal 721302, India.
LA  - eng
PT  - Journal Article
DEP - 20171012
PL  - United States
TA  - ACS Omega
JT  - ACS omega
JID - 101691658
PMC - PMC6045338
COIS- The authors declare no competing financial interest.
EDAT- 2018/07/20 06:00
MHDA- 2018/07/20 06:01
PMCR- 2017/10/12
CRDT- 2018/07/20 06:00
PHST- 2017/07/03 00:00 [received]
PHST- 2017/09/27 00:00 [accepted]
PHST- 2018/07/20 06:00 [entrez]
PHST- 2018/07/20 06:00 [pubmed]
PHST- 2018/07/20 06:01 [medline]
PHST- 2017/10/12 00:00 [pmc-release]
AID - 10.1021/acsomega.7b00911 [doi]
PST - ppublish
SO  - ACS Omega. 2017 Oct 31;2(10):6677-6690. doi: 10.1021/acsomega.7b00911. Epub 2017 
      Oct 12.