Synthesis of dopamine-functionalized quantum graphene dot-dopamin-hyaluronic acid nanocomposite loaded with parthenolide and assessment of its impact on cancer cells: an in vitro model

Abstract Background and aims Nanocarriers can enhance the delivery of parthenolide (PTL) to cancer cells while reducing toxicity to normal tissues. We developed Dopamine-Functionalized Quantum Graphene Dot-Dopamin-Hyaluronic Acid Nanocomposite Loaded with PTL (GQD-DA-HA-PTL NCs) and assessed their cytotoxic, apoptotic, and antioxidant effects in vitro on MCF-7 and other cancer cell lines (HCT116, A2780, HepG2, HeLa), and compared these results with those obtained from normal human dermal fibroblasts (HDF). Methods GQD-DA-HA-PTL NCs were synthesized and characterized by DLS, FESEM, and FTIR. Encapsulation efficiency and PTL release were measured at 219 nm. Cytotoxicity was evaluated via MTT in cancer cell lines (0–125 µg/mL) after 48 h. Apoptosis was assessed with Annexin V-FITC/PI and AO/PI staining. Mechanistic insights included real-time PCR for NF-κB, p53, caspase-8, and caspase-9. Antioxidant capacity was measured using ABTS and DPPH scavenging assays, as well as an SOD1 activity assay. Results GQD-DA-HA-PTL NCs exhibited high PTL encapsulation and sustained release. They demonstrated strong cytotoxicity against MCF-7 cells, with an IC50 lower than that of free PTL, and reduced toxicity to HDF cells. The GQD-DA-HA-PTL NCs reduced viability across other cancer cell lines, particularly HeLa and HCT116, with minimal effects on HepG2. Apoptosis was confirmed as the primary cell death mechanism, with real-time PCR showing upregulation of NF-κB, p53, and caspase-9, indicating activation of intrinsic apoptotic pathways. Antioxidant assays demonstrated significant radical-scavenging activity and increased SOD1 levels. Conclusion GQD-DA-HA-PTL NCs exhibit appropriate in vitro cytotoxicity against multiple cancer cell lines with selectivity over normal cells, accompanied by apoptosis induction and antioxidant modulation. While these findings support the potential of this nanodelivery system to enhance PTL efficacy, further studies are required to clarify mechanistic details and to evaluate safety and efficacy in more complex models.