Antitumoral activities of λ‑carrageenan oligosaccharide- based nanoparticles.

Polysaccharides (PS) are key building blocks for bioactive nanomaterials in oncology, as they enhance colloidal stability, enable chemical functionalization, support controlled delivery systems, and, for selected families, provide targeting or therapeutic activities. However, despite their high biomedical potential, PS families such as λ-carrageenan (λ-CAR) have remained virtually unexplored in nano-oncology, as poor solubility, restrictive rheological properties, and undesired anticoagulant and pro-inflammatory effects constitute a major barrier to systemic use in vivo. In a recent study, we showed that depolymerized λ-carrageenan oligosaccharides (λ-COS) overcome these limitations and enable the design of stable hybrid nanoparticles embedding free Mn²⁺ ions and ultrasmall ferrite cores (λ-COS NP), exhibiting excellent colloidal stability, in vivo compatibility, and efficient MRI contrast capabilities. Building on this work, the present study investigates the inherent antitumor potential of these "unlocked" λ-COS NP, harnessing the known complementary bioactive properties of the λ-COS scaffold and those of the ferrite/Mn2+ cargo. The λ-COS NP effectively inhibited the migration of MDA-MB-231 triple-negative breast cancer cells and suppressed heparanase (HPSE) activity, a key enzyme involved in tumor invasiveness. Moreover, λ-COS NP were efficiently internalized by RAW 264.7 macrophages and reprogrammed M2-like polarized cells toward an antitumor phenotype by restoring TNF-α and nitric oxide production. Preclinical studies in an MDA-MB-231 xenograft mouse model revealed efficient tumor accumulation and MRI detectability following intravenous administration, and a 50% reduction in tumor growth at the end of the therapeutic assays. Collectively, these results highlight λ-COS NP as promising tumor microenvironment-targeted nanotherapeutics with integrated bioactivities and imaging-tracking potential.