Formulation and immunomodulatory activity of innovative folic acid-targeted β-glucan nanocarriers in colorectal carcinoma

To address the safety and specificity limitations of conventional chemotherapy, this study developed a novel folic acid-modified β-glucan (LNT-FA) nanodelivery system to enhance the therapeutic efficacy of doxorubicin (DOX). Leveraging the intrinsic immunomodulatory properties of β-glucan, DOX-loaded triple-helix nanoparticles were successfully constructed via solvent-regulated self-assembly. Physicochemical characterization revealed that the DOX@LNT-FA nanoparticles possessed a hydrodynamic diameter of 98.62 ± 0.60 nm, an encapsulation efficiency of 38.1 ± 0.38%, and a drug loading capacity of 9.45 ± 0.24%. Furthermore, the nanoparticles exhibited excellent pH-sensitive release profiles, superior biocompatibility, and active targeting capability. Notably, in vivo studies confirmed that DOX@LNT-FA significantly inhibited tumor growth with an impressive inhibition rate of 86%, while effectively mitigating the systemic toxicity associated with free DOX. Mechanistically, the nanoparticles suppressed the NF-κB signaling pathway, which is strongly associated with β-glucan's immunomodulatory function, to produce anticancer effects. Collectively, this β-glucan-based nanosystem synergistically combines high drug loading with immunomodulatory effects, offering a safe and precise strategy with significant potential for clinical translation in cancer therapy.