Carbon nano-onions for biomedical applications Silvia Giordani DCU, Ireland
There are many issues associated with free drug delivery including: adverse side-effects, multi-drug resistance, premature drug degradation, lack of tissue penetration, and non-specific toxicity. Targeted delivery, which utilizes nanocarriers as payload delivery vesicles, has the potential to address and alleviate these prominent issues. Specifically, it involves nanomaterials functionalized with targeting agents, allowing for the selective uptake of these nanocarriers by cells overexpressing specific receptors. This approach explicitly increases the drug concentration in the target cell of interest whilst minimizing the exposure of healthy cells to the therapeutic agent. In this presentation, carbon nano-onions (CNOs) will be discussed as a potential vesicle for nanocarrier-type drug delivery systems. 1 CNOs, or multi-layer fullerenes, consist of multiple concentric layers of sp2 hybridized carbon and are emerging as platforms for biomedical applications because of their ability to be internalized by cells and low toxicity. 2 In my research group we have developed methodology for the synthesis of pure, monodispersed CNOs and various chemical functionalization strategies for the introduction of different functionalities (receptor targeting unit and imaging unit) onto the surface of the CNOs. The modified CNOs display high brightness and photostability in aqueous solutions and are selectively taken up by different cancer cell lines without significant cytotoxicity. Supramolecular functionalization with biocompatible polymers is an effective strategy to develop engineered drug carriers for targeted delivery applications. We reported the use of a hyaluronic acid-phospholipid (HA-DMPE) conjugate to target CD44 overexpressing cancer cells, while enhancing solubility of the nanoconstruct. Non- covalently functionalized CNOs with HA-DMPE show excellent in vitro cell viability in human breast carcinoma cells overexpressing CD44 and are uptaken to a greater extent compared to human ovarian carcinoma cells with an undetectable amount of CD44. In addition, they possess high in vivo biocompatibility in zebrafish during the different stages of development suggesting a high degree of biosafety of this class of nanomaterials. 3 We recently synthesized Boron/nitrogen co-doped carbon nano-onions (BN-CNOs) 4 and examined their interactions with biological systems. Our study on the toxicological profiles of BN-CNOs and oxidized BN-CNOs in vitro in both healthy and cancer cell lines, as well as in vivo on the embryonic stages of zebrafish (Danio rerio) demonstrate that these new class of carbonnanoparticles have high cyto-biocompatibility and a high biosafety. 5 Non covalent functionalization of BN-CNOs with HA-DMPE gave dispersions with long term aqueous stability. 6 Our results encourage further development as targeted diagnostics or therapeutics nanocarriers. References
1. M. Bartkowski and S. Giordani, Dalton Transactions 2021, 50 (7), 23. 2. S. Giordani et al., Current Medicinal Chemistry 2019, 26 (38), 6915. 3. M d’Amora et al., Colloids and Surfaces B: Biointerfaces 2020, 110779. 4. A. Camisasca et al., ACS Applied NanoMaterials 2018, 1, 5763.
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