Photoresponsive Block Copolymer Prodrug Nanoparticles as Delivery Vehicle for Single and Dual Anticancer Drugs Gargi Biswas Bikash Chandra Jena Saikat Maiti Pousali Samanta Mahitosh Mandal Dibakar Dhara 10.1021/acsomega.7b00911.s001 https://acs.figshare.com/articles/journal_contribution/Photoresponsive_Block_Copolymer_Prodrug_Nanoparticles_as_Delivery_Vehicle_for_Single_and_Dual_Anticancer_Drugs/5492434 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)-<i>b</i>-poly­(HMNPPA)-<i>b</i>-poly­(PEGMA-<i>stat</i>-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. 2017-10-12 08:14:57 BA Photoresponsive Block Copolymer Prodrug Nanoparticles HMNPPA release cancer cells drug-loaded micellar nanoparticles Confocal microscopy results cancer cell-targeted polymer prodrug DDS photolabile ester bond transmission electron microscopy measurements UV prodrug micellar nanoparticles polymer prodrug Nile Red fluorescence addition fragmentation chain transfer polymerization Cbl Dual Anticancer Drugs DOX-loaded nanoparticles drug delivery systems