Platelet membrane cloaked pectin and iron oxide based hybrid nanoparticles for the treatment of colorectal cancer and associated anemia.

Colorectal cancer (CRC) accompanied by iron deficiency anemia presents a significant therapeutic challenge, necessitating treatment strategies that simultaneously suppress tumor progression and restore iron homeostasis. Herein, a biomimetic multifunctional hybrid nanoparticle (HYB-NPs) platform was developed for the concurrent treatment of CRC and anemia. Gemcitabine was encapsulated within pectin nanoparticles and subsequently coated with platelet membranes through mild sonication to improve tumor-targeted delivery. Molecular docking demonstrated strong interactions between platelet membrane proteins and CD44 receptors, supporting receptor-mediated tumor recognition. Biogenic iron oxide nanoparticles were further integrated onto the platelet membrane-coated nanoparticles via calcium-mediated bridging, thereby enabling simultaneous chemotherapy and iron supplementation. The optimized HYB-NPs exhibited a particle size of 182 ± 2 nm, a zeta potential of -30.8 ± 2.6 mV, and high encapsulation efficiencies for gemcitabine (82 ± 2.0%) and iron (86 ± 1.0%), indicating excellent physicochemical stability. Characterization using Fourier transform infrared spectroscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, and scanning electron microscopy confirmed successful nanoparticle fabrication, structural integrity, elemental composition, and spherical morphology. In vitro studies revealed sustained tumor-responsive gemcitabine release, controlled iron release, enhanced cellular uptake, and superior cytotoxicity against HT-29 cells. HYB-NPs also induced apoptosis and favorably modulated inflammatory cytokines, supporting restoration of antitumor immune responses. In vivo studies demonstrated excellent biocompatibility, prolonged systemic circulation, significant tumor inhibition (87.5 ± 1.2%), improved survival, and restoration of iron homeostasis in a 1,2-dimethylhydrazine-induced CRC model. These findings highlight HYB-NPs as a promising biomimetic nanoplatform for targeted CRC therapy with simultaneous anemia management.