Abstract
The simultaneous delivery of therapeutic agents and imaging probes using polymeric nanoparticles (NPs) has gained significant attention for cancer treatment. In this work, we developed a multifunctional nanocarrier system composed of an amphiphilic block copolymer, poly-(2-ethyl-2-oxazoline)-b-poly-(ε-caprolactone) (PEtOx-b-PCL), and dimethyldidodecylammonium bromide (DDAB), for the codelivery of the chemotherapeutic drug pemetrexed (PMT) and nitrogen- or sulfur-doped graphene quantum dots (N-GQDs or S-GQDs) as fluorescent probes. Critical formulation parameters were optimized using a central composite design (CCD). The optimized NPs exhibited favorable physicochemical properties, including positive surface charge (6-8 mV), hydrodynamic diameters of ∼140 nm, and high encapsulation efficiency for both PMT (46-56%) and GQDs (>98%). In vitro assays revealed that PMT-loaded nanoparticles (NPs) significantly enhanced cytotoxicity against MCF-7 cells. At a concentration of 2 ppm after 72 h, N-PMT NPs and S-PMT NPs inhibited cell proliferation by 50.7% and 53.8%, respectively, compared to 37.8% inhibition with free PMT at the same dose. Confocal microscopy confirmed efficient intracellular uptake and strong fluorescence signals, supporting their potential for bioimaging. Collectively, these results demonstrate that this two-in-one nanocarrier system significantly enhances chemotherapeutic efficacy while enabling real-time imaging, establishing a promising platform for drug delivery and noninvasive treatment monitoring in cancer nanomedicine.