Synthesis and Characterization of a Fullerenol Derivative for Potential Biological Applications

Abstract

Several biological barriers are generally responsible for the limited delivery of cargoes at the cellular level. Fullerenols have unique structural features and possess suitable properties for interaction with the cells. This study aimed to synthesize and characterize a fullerenol derivative with desirable characteristics (size, charge, functionality) to develop cell penetration vehicles. Fullerenol was synthesized from fullerene (C60) solubilized in toluene, followed by hydroxylation with hydrogen peroxide and tetra-n-butylammonium hydroxide (TBAH) as a phase transfer catalyst. The obtained product was purified by a Florisil chromatography column (water as the eluent), followed by dialysis (cellulose membrane dialysis tubing) and freeze-drying (yield 66%). Subsequently, a silane coupling agent was conjugated on the fullerenol surface to render free amine functional groups for further covalent functionalization with other molecules. Characterization via UV–VIS, FTIR-ATR, Raman, DLS, and SEM techniques was conducted to evaluate the composition, size, morphology, surface functionality, and structural properties. We are currently working on the conjugation of the potent cell-penetrating agents Buforin II (BUFII) and the Outer Membrane Protein A (OmpA) on the surface of the fullerenol to estimate whether cell penetration and endosome escape are improved concerning conventional polymeric vehicles and our previous developments with iron oxide nanoparticles.

Unlocking cellular barriers: silica nanoparticles and fullerenol conjugated cell-penetrating agents for enhanced intracellular drug delivery

“…In the as-synthesized fullerenol, the two peaks observed at 2,963 and 2,873 cm –1 (C-H st ) were attributed to residual TBAH ( Kokubo et al, 2011 ). Purified fullerenol showed a broad band at around 3,424 cm –1 (O-H st ) and four characteristic bands at 1,598 cm –1 (C=C st ), 1,410 cm –1 (O-H b ), 1,352 cm –1 (C-O-H b ), and 1,112 cm –1 (C-O st ), which agree well with previously reported data ( Kokubo et al, 2011 ; Ravelo-Nieto et al, 2020 ). Silanization was confirmed by the presence of new bands at 2,964 cm –1 (C-H st as ), 2,934 cm –1 (C-H st sy ), 2,875 cm –1 (H-C (-N) st ), 1,564 cm –1 (N-H b ), and 1,344 cm –1 (C-N st ), which can be attributed to propylamine groups.…”

Effects of Carbon Nanomaterials and Aloe vera on Melanomas—Where Are We? Recent Updates

“…Studies have shown improved performance associated with the application of NPs delivery mechanisms, and some of these drugs have been approved by the FDA and are already part of antineoplastic clinical practice, including the drugs doxorubicin, cisplatin, paclitaxel, vincristine, and cyclodextrin. The most commonly used nanomaterials in these nanoformulations are liposomes, dendrimers, CNTs, inorganic NPs, micelles, magnetic NPs, and CQDs [ 18 , 92 , 93 , 112 , 151 ].…”

“…In addition, fullerenol synthesized from fullerene (C60) represents a promising candidate for the carrier effect as a “molecular chassis”, due to the enhanced cellular uptake and endosomal escape compared to other conventional polymeric vehicles. In this context, fullerenes possess unique structural features and properties suitable for cell–cell interactions, which are essential for biological and biomedical applications and depend on features such as size, charge, and functionalization, due to their efficient interactions with biomolecules [ 93 ].…”

“…Similarly, [Gd@C 82 (OH) 22 ] nanoparticles show high antitumor efficiency in a variety of cancer xenograft models, such as liver cancer (H22 and HepG2 cells), human microvascular endothelial cells, and MCF-7 cells [ 89 ]. Interestingly, Gd@C 82 (OH) 22 acts indirectly by “blocking” the tumor through adjustments of biomolecules that act together with the tumor microenvironment rather than by directly destroying the tumor [ 93 , 94 ]. Similarly, fullerene derivatives not only exert anticarcinogenic activity by regulating multiple steps in the crucial bioprocesses of carcinogenesis, including tumor growth and the metastasis of melanoma, breast carcinoma, prostate carcinoma, and leukemia, but also activate the patient’s immune system to eliminate these cancer cells ( Figure 3 a) [ 89 , 95 ].…”

“… Carbon-based nanomaterials and their main biological activities for therapeutic and theranostic applications. ( a ) Fullerene [ 89 , 90 , 91 , 92 , 93 , 94 , 95 ]; ( b ) Graphene, graphene oxide [ 96 , 98 , 100 ]; ( c ) Carbon nanotubes [ 104 , 105 , 106 , 108 , 110 , 111 ]; ( d ) Carbon nanofibers [ 114 , 116 , 117 , 118 ]; ( e ) Carbon nanohorm [ 120 , 121 , 122 , 123 ]; ( f ) Quantum dots [ 125 , 126 , 128 , 131 ]; ( g ) Nanodiamonds [ 128 , 129 , 130 , 131 ]. …”