Curcumin-crosslinked single-chain polymer nanoparticles as potential polymer-drug conjugates

Abstract

Single-chain polymer nanoparticles (SCNPs) conjugated with curcumin were developed via Williamson etherification, offering a promising platform for drug delivery. Poly[(poly(ethylene glycol) methyl ether methacrylate)-r-(2-bromoethyl methacrylate)] was synthesized by reversible addition-fragmentation chain- transfer (RAFT) polymerization, with an 80:20 ratio chosen for optimal properties. Curcumin conjugation to 2-bromoethyl methacrylate (BEMA) units was confirmed through UV-Vis and NMR spectroscopy. The obtained SCNPs exhibited reduced molecular weights and hydrodynamic diameters (<7.66 nm) compared to their polymer precursors as confirmed by GPC and DLS. TEM analyses revealed that the obtained SCNPs exhibited spherical morphology. SCNP-2 exhibited pH-responsive curcumin release, with a cumulative release of 48% at pH 5.0 and 8% at pH 7.4 over 20 d. Cellular uptake studies revealed significant SCNP-2 accumulation in MDA-MB-231 cells. Cytotoxicity assays showed selective toxicity against cancer cells, while the polymer alone exhibited no cytotoxicity, highlighting its safety. These findings suggest that curcumin-conjugated SCNPs have potential as targeted cancer therapy agents.