Photoresponsive Block Copolymer Prodrug Nanoparticles
as Delivery Vehicle for Single and Dual Anticancer Drugs
Posted on 2017-10-12 - 08:14
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 (λ ≥ 365 nm) and laser (λ
= 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.
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Biswas, Gargi; Jena, Bikash Chandra; Maiti, Saikat; Samanta, Pousali; Mandal, Mahitosh; Dhara, Dibakar (2017). Photoresponsive Block Copolymer Prodrug Nanoparticles
as Delivery Vehicle for Single and Dual Anticancer Drugs. ACS Publications. Collection. https://doi.org/10.1021/acsomega.7b00911
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AUTHORS (6)
GB
Gargi Biswas
BJ
Bikash Chandra Jena
SM
Saikat Maiti
PS
Pousali Samanta
MM
Mahitosh Mandal
DD
Dibakar Dhara
KEYWORDS
BAPhotoresponsive Block Copolymer Prodrug NanoparticlesHMNPPAreleasecancer cellsdrug-loaded micellar nanoparticlesConfocal microscopy resultscancer cell-targeted polymer prodrugDDSphotolabile ester bondtransmission electron microscopy measurementsUVprodrug micellar nanoparticlespolymer prodrugNile Red fluorescenceaddition fragmentation chain transfer polymerizationCblDual Anticancer DrugsDOX-loaded nanoparticlesdrug delivery systems