Anti-carcinoembryonic antigen conjugated resveratrol/sunitinib-loaded polymeric nanoparticles for therapeutic enhancement in colorectal cancer

Abstract

Colorectal cancer treatment remains limited by poor tumor selectivity, systemic toxicity, and insufficient delivery of combination therapies to three-dimensional tumor-like structures. This study investigates the development and application of anti-carcinoembryonic antigen (anti-CEA) conjugated polymeric nanoparticles co-loaded with sunitinib (SUN) and resveratrol (RSV) for the treatment of colorectal cancer. The nanoparticles, formulated using poly(lactic-co-glycolic acid) (PLGA), exhibited favorable physicochemical properties, including a particle size of 207.6 ± 19.0 nm and a negative surface charge of −24.8 ± 0.7 mV. The nanoparticles exhibited controlled and sustained drug release, enabling the prolonged therapeutic efficacy of SUN and RSV. Functionalization with anti-CEA antibodies enabled selective targeting of colorectal cancer cells, as demonstrated by enhanced internalization in HCT-116 cells with high CEA expression. Consistent with this targeting effect, the anti-CEA-conjugated nanoparticles achieved a 29% relative reduction in cell viability against HCT-116 cells compared to non-targeted counterparts in two-dimensional cultures. Furthermore, the SUN and RSV combination exhibited potent synergistic effects across three-dimensional spheroid models. The anti-CEA functionalized system proved more effective, reducing spheroid volume and cell viability by 10% and 14%, respectively, compared to the non-targeted nanoparticles. These findings highlight the potential of CEA-targeted polymeric nanoparticles for co-delivery of synergistic anticancer agents, offering a promising strategy for colorectal cancer therapy.