Biogenic Carbon Quantum Dots: A Green Glucuronic-Acid-Functionalized Nanosystem for pH-Responsive Dual-Drug Delivery in Glioblastoma

Glioblastoma multiforme (GBM) is an incurable primary brain malignancy characterized by prominent chemoresistance and poor prognosis. Herein, we report an in vitro proof-of-concept study of a green, ligand-functionalized carbon quantum dot (CQD) for combined drug delivery with pH-responsive release in glioblastoma cells. Nitrogen-doped red-emissive N-CQDs were synthesized via a hydrothermal method using locust biomass as a renewable carbon precursor, functionalized with glucuronic acid for active tumor targeting, and loaded with piperlongumine (PL) and silibinin (SIL) drugs at an optimized mass ratio. The nanosystem was characterized by XRD, FTIR, SEM, TEM, XPS, and optical spectroscopy, and evaluated in vitro for drug release, cellular uptake, apoptosis, ROS levels, and caspase-3 activity. The optimized nanoplatform exhibited uniform morphology (average size 2.76 nm), strong red fluorescence (Ex490nm/Em620nm), high dual-drug loading efficiency (46.0%), and pH-responsive release behavior with rapid drug liberation in the acidic tumor microenvironment (pH 5.5) and minimal leakage at physiological pH (pH 7.4). The nanosystem demonstrated efficient cellular internalization, dual mitochondrial/nuclear targeting, and enhanced combined antitumor effect via ROS overproduction and activation of the caspase-3 pathway. This work establishes a green and multifunctional nanotherapeutic platform with promising potential for future glioblastoma-directed drug delivery applications.