Engineering Dual-Loaded PLGA Nanoparticles with Gold Nanorods and Doxorubicin as Robust Multimodal Nanoplatforms

Given the complexity of cancer, combination approaches such as chemo-photothermal and image-guided therapies are increasingly explored, driving interest in nanocarriers that integrate multiple structural abilities within a single platform. Here, we report a dual-functional nanoplatform in which gold nanorods (AuNRs) and doxorubicin (DOX) are coencapsulated in poly-(lactic-<i>co</i>-glycolic acid) (PLGA) nanoparticles (mean diameter ≈ 246 nm) after optimizing the amount of gold nanorods to be encapsulated. The dual-loaded nanoformulation yields a narrow size distribution (PDI ≤ 0.1), an adequate DOX level (32 ± 4 μg mL^-1) for chemotherapeutic efficacy, and sufficient Au content (encapsulation efficiency of 48%) to achieve an enhanced temperature increase under NIR irradiation. Comprehensive stability testing for both AuNR-encapsulated PLGA Nps and bare-PLGA Nps was performed. Continuous centrifugation-redispersion cycles and 110-day storage at 4 °C reveal no measurable aggregation, shape deformation, or LSPR dampening in PLGA-encapsulated AuNRs, whereas free AuNRs lost their signal under the same conditions. Upon 808 nm irradiation (1 W cm^-2, 5 min) the PLGA-Au-DOX nanospheres create ∼25 °C temperature difference, confirming intact photothermal performance. MTT assays in MCF-7 human breast cancer cells show that cytotoxicity is dominated by the chemotherapeutic payload in the designed system. The findings after detailed gold nanorod encapsulation optimization and stability studies indicate that the resulting nanoparticle is a well-characterized, dual-loaded, and reliable nanocarrier candidate for future in vivo studies on dual-modality cancer theranostics.