Host–Guest Encapsulation of Fullerenes by Lys-2Gly Dendrimers: Physicochemical Characterization and In Vitro Cytotoxicity Evaluations

Abstract We investigate the physicochemical properties of complexes formed between the peptide Lys-2Gly dendrimer and C60 and C70 fullerenes. Combining small-angle X-ray scattering (SAXS), dynamic light scattering (DLS), NMR, and molecular dynamics (MD) simulations, we reveal a pronounced structural compaction upon encapsulation. Both the radius of gyration and the hydrodynamic radius of the dendrimer-fullerene complexes are significantly reduced compared to the free dendrimer. DLS measurements corroborate these results, indicating that the complexes remain monodisperse and free of aggregates. To assess the biocompatibility of these nanocarriers, we evaluated their cytotoxicity in vitro across cancer (HeLa G63, HT-1080) and normal (dermal fibroblasts) human cell lines. The complexes exhibit low cytotoxicity at physiologically relevant concentrations. Cytotoxicity remains low but becomes measurable in a concentration-, time-, and cell-line-dependent manner at supraphysiological doses (≥100 μg/mL). Notably, both compounds demonstrated enhanced cytotoxicity toward the HT-1080 cancer cell line at high concentrations, while showing moderate toxicity in normal cells. These findings highlight the Lys-2Gly dendrimer as a robust, biocompatible nanoplatform, indicating its potential for the encapsulation and delivery of hydrophobic therapeutics and contrast agents.