Thermal, pH, and Photo Multistimuli Responsive Block Copolymer Self-Assembly Nanoparticles for Drug Delivery Using Visible-Light-Induced PET-RAFT

Abstract

Stimuli-responsive polymeric drug delivery nanocarriers potentially allow for drug release profiles in a spatiotemporal manner via multistimuli, either exogenous or endogenous. In this study, poly( N -isopropylacrylamide- co - N, N -dimethylacrylamide- b -glycidyl methacrylate) (P(NIPAM- co -DMA)- b -PGMA) was first synthesized through photoinduced electronic transfer reversible addition-fragmentation chain transfer (PET-RAFT) polymerization, using Eosin Y and 5,10,15,20-tetraphenyl-21 H,23 H -porphine zinc (ZnTPP) as photocatalysts under visible-light irradiation at room temperature. The polymer was then functionalized with 4-(phenylazo)phenol (Azo). Gel permeation chromatography characterization confirmed the efficient PET-RAFT polymerization of NIPAM with low dispersity (PDI, Đ < 1.35), temporal control, and chain-end fidelity, achieved under blue-light irradiation (λ max = 420 nm, 24 mW/cm 2 ). The subsequent blocking of PGMA on the P(NIPAM- co -DMA) chain was successfully accomplished with red-light irradiation (λ max = 625 nm, 5.8 mW/cm 2 ). After Azo grafting to the epoxy groups, a thermal, pH, and photo multistimuli responsive polymer was self-assembled in water, with a curcumin encapsulation efficiency of 90%, and particle morphologies observed with sizes ranging from 220 to 600 nm. The nanoparticles exhibited a lower critical solution temperature value (LCST) of 38.09 °C, and could undergo trans/cis isomerization of the azobenzene structure under UV irradiation. As a result, the nanoparticles demonstrated significant responsiveness to pH, UV, and heat stimuli. Curcumin was smoothly released under UV exposure and/or at 50 °C, with a release ratio of over 80% within 3 h. Additionally, rapid curcumin release was observed in an alkaline environment. Overall, the visible-light-induced PET-RAFT polymerization technique shows great potential in the controlled synthesis of multiresponsive intelligent drug delivery nanocarriers.