Photoluminescent folic acid functionalized biocompatible and stimuli-responsive nanostructured polymer brushes for targeted and controlled delivery of doxorubicin

Abstract

In this work, the new photoluminescent and biocompatible folic acid (FA) conjugated stimuli-responsive nanostructured polymer brushes were designed, fabricated, and then evaluated as a doxorubicin (DOX) carrier. In this regard at first, graphene quantum dots (GQDs) were prepared through citric acid (CA) pyrolysis. In the following, the functionalization of GQDs with 3-aminopropyltriethoxysilane (APTS) and then α-bromoisobutyryl bromide (BIB) obtained the GQDs-Br, which have the ability to acts as a nano-based initiator. Subsequently, the N-isopropylacrylamide (NIPAM) and acrylated β-cyclodextrin (Ac-β-CD) monomers grown from the GQDs-Br surface as a block copolymer (GQDs-PNIPAM-co-PβCD) via atom transfer radical polymerization (ATRP) technique. Eventually, the conjugation with FA achieved the photoluminescent nanostructure copolymer brushes with targeted drug delivery capability (GQDs-PNIPAM-co-PβCD@FA). The synthesized samples were characterized through various characterization techniques. DOX was loaded via several possible interactions on GQDs-PNIPAM-co-PβCD@FA. The in vitro DOX release test exhibited 12% of DOX release in the simulated environment with the physiological condition while 43% of DOX released in the simulated cancer cells condition; confirm the pH sensitivity of the carrier. The in vitro biological tests displayed good stability, biodegradability, and biocompatibility of the prepared nanostructure. As well as, the higher efficiency of DOX@GQDs-PNIPAM-co-PβCD@FA in MDA-MB 231 cells killing compared to A 549 cells revealed the targeted drug delivery. The results demonstrated that the fabricated nanosystem could be a hopeful candidate for targeted breast cancer therapy with the inherent potential of imaging.