Biological applications of hydrophilic C60 derivatives (hC60s)− a structural perspective

Abstract

Abstract:Reactive oxygen species (ROS) generation and radical scavenging are dual properties of hydrophilic C60 derivatives (hC60s). hC60s eliminate radicals in dark, while they produce reactive oxygen species (ROS) in the presence of irradiation and oxygen. Compared to the pristine C60 suspension, the aqueous solution of hC60s is easier to handle in vivo. hC60s are diverse and could be placed into two general categories: covalently modified C60 derivatives and pristine C60 solubilized non-covalently by macromolecules. In order to present in detail, the above categories are broken down into 8 parts: C60(OH)n, C60 with carboxylic acid, C60 with quaternary ammonium salts, C60 with peptide, C60 containing sugar, C60 modified covalently or non-covalently solubilized by cyclodextrins (CDs), pristine C60 delivered by liposomes, functionalized C60-polymer and pristine C60 solubilized by polymer. Each hC60 shows the propensity to be ROS producer or radical scavenger. This preference is dependent on hC60s structures. For example, major application of C60(OH)n is radical scavenger, while pristine C60/γ-CD complex usually serves as ROS producer. In addition, the electron acceptability and innate hydrophobic surface confer hC60s with O2 uptake inhibition, HIV inhibition and membrane permeability. In this review, we summarize the preparation methods and biological applications of hC60s according to the structures.

Design, synthesis and biological evaluation of water-soluble per-O-methylated cyclodextrin-C60 conjugates as anti-influenza virus agents

“…However, the emergence of drug-resistant influenza viruses has limited the use of those drugs, illustrating the urgent need to develop novel anti-influenza drugs [2,3]. C60 serves as radical scavenger, reactive oxygen species (ROS) producer under irradiation, human immunodeficiency virus (HIV) and hepatitis C virus (HCV) inhibitors, O2 uptake inhibitor, drug and DNA vectors [4,5]. Nevertheless, its poor water-solubility limits the further development of C60.…”

C60@lysozyme: a new photosensitizing agent for photodynamic therapy

“…[2][3][4][5] In the last decade, fullerenes have gained considerable attention as potentials photosensitizer for PDT of various diseases. Fullerenes possess considerable advantages over the traditional photosensitizer used in photodynamic therapy: i) Fullerenes are highly photostable and undergo less photobleaching compared to the traditional dyes used in PDT; [2][3][4][5][6][7][8][9][10][11] ii) Fullerenes follow both the photophysical mechanisms, while the traditional dyes show mainly type II mechanism; [2][3][4][5][6][7][8][9][10][11] iii) The reactive oxygen species production yield is close to unity; [2][3][4][5][6][7][8][9][10][11] However, the use of fullerenes in PDT still presents important restrictions in their application due to the dependency of their properties and toxicity on the physiological environment and the related aggregation phenomena 65 and their poor water solubility and low biocompatibility; 65 Monodispersity of fullerenes is the crucial feature for potential application in PDT: 12,14,65 Aggregation is a well-known factor that could deactivate the excited electronic states of photosensitizers. [2][3]…”

“…When fullerenes aggregates are present, 3 C60* can be easily quenched by the surrounding C60 or by other 3 C60* (triplet-triplet annihilation) and, consequently, the lifetime is drastically reduced (from a hundreds of µs for monomeric C60 to less than 0.1 µs in a C60 aggregate). [2][3][4][5][6][7][8][9][10][11] In addition aggregation reduces also the active surface area of C60 in contact with O2 for ROS production.…”

Secondary‐Rim γ‐Cyclodextrin Functionalization to Conjugate with C60: Improved Efficacy as a Photosensitizer

“…Water‐soluble C 60 derivatives serve as radical scavengers, reactive oxygen species (ROS) producers, O 2 uptake inhibitors, HIV inhibitors, and DNA or drug vectors . However, inherent aggregation of such C 60 conjugates in polar solvents is a bottle‐neck in their therapeutic developments, as it prevents C 60 from interacting molecularly with the target and decreases the photoproduction efficacy of ROS . To enhance the photosensitivity of C 60 , It is necessary to prevent C 60 aggregation and enhance its water solubility.…”