Development and characterization of a novel pH-Responsive nanocarrier for enhanced quercetin delivery and cytotoxicity in lung cancer

A) Schematic of CS/HNTs/GQDs hydrogel loaded with QC, (B) Preparation steps of CS/HNTs, CS/ GQDs and CS/HNTs/GQDs hydrogel loaded by QC. [Display omitted] •Quercetin’s low bioavailability and high toxicity limit its use.•A pH-responsive nanocarrier using chitosan, halloysite nanotubes, and graphene quantum dots was developed.•Adding halloysite nanotubes to chitosan/graphene quantum dots improved drug loading and encapsulation efficiency.•Graphene quantum dots enhanced quercetin release from the composite.•The nanocarrier with quercetin showed high cytotoxicity against A549 lung cells. Quercetin (QC) is a potent polyphenol with numerous health benefits, but its use is limited due to its low bioavailability and high toxicity. Accordingly, a pH-responsive nanocarrier was created using chitosan (CS), halloysite nanotubes (HNTs), and graphene quantum dots (GQDs). It was found that LE and EE values of the CS/GQDs nanocomposites were 32.0% and 69.0%, respectively, increasing to 44.25% and 85.5% upon HNTs addition. The QC release study of pH-responsive CS/HNTs/GQDs nanocomposite in buffer environments showed that with the presence of GQDs in the CS/HNTs composite, the release rate increased from 73% and 54% at pH 5.4 and 7.4 to 97.5% and 67%. Examining the release data with kinetic models showed that the data corresponded to the first-order model, which indicates concentration-dependent drug release. In this study, the cytotoxicity of CS/HNT, CS/HNTs/GQDs, and CS/HNTs/GQDs@QC nanocomposites against L929 and A549 lung cell lines was investigated. The results showed that CS/HNTs/GQDs@QC had the highest cytotoxicity and had a more profound effect on A549 cells. The proportion of apoptotic cells in the CS/HNTs/GQDs@QC group was also higher than in the control group, with early and late apoptosis of 74.4% and 5.15%, respectively.