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Published on 13/10/2020
Fullerenes are subject of ongoing research as they possess unique geometrical shapes, as well as appealing photochemical, electrochemical and physical properties. In addition, they act as efficient radical scavenger and antioxidant, as well as nano carrier for gene and drug delivery. Thus, a wide variety of operations can be considered.
Amongst them, biological applications were promoted by the work of Friedman et al. in 1993, which showed that fullerene fits seamlessly the hydrophobic cavity of the human immunodeficiency virus (HIV)-1 protease, thus inhibiting the access of substrates to the catalytic site of the enzyme. This discovery highlighted the great potential of fullerenes as anti-HIV-1 agents and their significance for further pharmaceutical and biomedical applications.
Many neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease are caused by the hyper-production of certain radical species. Fullerenes can react with superoxide (O2·-) and hydroxyl (·OH) radicals, which otherwise harm the structural integrity of e.g. proteins and DNA. Due to this “radical scavenging reactivity”, Fullerenes and especially their poly-hydroxylated fullerenol derivatives are classified as “radical sponges”.
At the same time, another application benefits of the opposite effect. Photodynamic therapy (PD) is a therapeutic technique for the treatment of multiple diseases, e.g. cancer. An inactive photosensitizer (PS) is excited leading to the local generation of cytotoxic reactive oxygen species (ROS). As mentioned above, such radical species cause damage to various types of biomolecules and, most important, lead to the death of tumor cells. In this context, the photoirradiation of fullerenes to their triplet state leads to the production of singlet oxygen by the conversion of triplet oxygen in high quantum yields.
Besides their direct bioactivity, fullerenes can also serve as carbon-based nanocages for the targeted delivery of therapeutic molecules, e.g. for nucleic acid delivery, benefiting of their nonimmunological reactions. In addition, fullerene and its derivatives show high potential in crossing the blood-brain barrier and delivering drugs into the CNS.
Nevertheless, one major issue concerning biomedical applications remains the bad solubility of fullerene itself in aqueous solutions. The most promising classes of water-soluble derivatives are carboxylated or the already mentioned polyhydroxylated fullerenol derivatives, which are both part of Iris Biotech’s portfolio. Furthermore, the advertised C60 and C70 fullerenes react with nucleophiles, e.g. the amino groups of amino acids, which improves their solubility. The functionalization of fullerenes allows the easy generation of conjugates with other biomolecules, or PEGs and linkers, to fulfill your required demands.
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