The rational design of nanoconjugate systems embodies significant relevance to developing precision medicine. Such precision benefits from a system with controllable functionalization as it allows for a consistent activity that can be reliably studied. Given its well-defined molecular structure and controllable surface functionalization, C60 represents a promising scaffold for the design of precise materials. Its higher organic character renders it accessible to organic reactions, and this carbon allotrope further benefits from inherent biocompatibility from its carbon-based framework, and from exohedral functionalization, which allows for therapeutic and biorthogonal ligand attachment. Our recent work has been aimed at synthesizing fullerene derivatives with symmetric and asymmetric ligands bearing some biological relevance concerning aqueous compatibility, drug delivery, fluorescence imaging, or photosensitization. Investigations into their cellular activity exhibited exciting results, particularly at the level of oxidative function in which a symmetrical hexakis fullerene derivative displayed potent antioxidant activity in-vitro. By varying the surface decoration on the cage, various factors, including multivalency, cage conjugation, and ligand charge, were found to modulate oxidative capacity. In addition to its anti-oxidative property, our work highlights the contrasting pro-oxidative property of fullerenes in the design of a fullerene-BODIPY dyad, which was constructed for the lysosomal targeting of aged cells. This design takes advantage of our previously reported results that demonstrated selective sub-cellular accumulation of differently functionalized C60 derivatives, and it provides an example of how our work in elucidating structure-function insights can be used for the targeted design of fullerene nanomaterials.

C60 as a modular platform for biomedicines

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