Functionalized fullerenes mediate photodynamic killing of cancer cells: Type I versus Type II photochemical mechanism (original) (raw)
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Photodynamic therapy with fullerenes
Photochemical & Photobiological Sciences, 2007
Fullerenes are a class of closed-cage nanomaterials made exclusively from carbon atoms. A great deal of attention has been focused on developing medical uses of these unique molecules especially when they are derivatized with functional groups to make them soluble and therefore able to interact with biological systems. Due to their extended π-conjugation they absorb visible light, have a high triplet yield and can generate reactive oxygen species upon illumination, suggesting a possible role of fullerenes in photodynamic therapy. Depending on the functional groups introduced into the molecule, fullerenes can effectively photoinactivate either or both pathogenic microbial cells and malignant cancer cells. The mechanism appears to involve superoxide anion as well as singlet oxygen, and under the right conditions fullerenes may have advantages over clinically applied photosensitizers for mediating photodynamic therapy of certain diseases. † The HTML version of this article has been enhanced with additional colour images.
Functionalized Fullerenes in Photodynamic Therapy
Journal of Biomedical Nanotechnology, 2014
Since the discovery of C 60 fullerene in 1985, scientists have been searching for biomedical applications of this most fascinating of molecules. The unique photophysical and photochemical properties of C 60 suggested that the molecule would function well as a photosensitizer in photodynamic therapy (PDT). PDT uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that kill unwanted cells. However the extreme insolubility and hydrophobicity of pristine C 60 , mandated that the cage be functionalized with chemical groups that provided water solubility and biological targeting ability. It has been found that cationic quaternary ammonium groups provide both these features, and this review covers work on the use of cationic fullerenes to mediate destruction of cancer cells and pathogenic microorganisms in vitro and describes the treatment of tumors and microbial infections in mouse models. The design, synthesis, and use of simple pyrrolidinium salts, more complex decacationic chains, and light-harvesting antennae that can be attached to C 60 , C 70 and C 84 cages are covered. In the case of bacterial wound infections mice can be saved from certain death by fullerene-mediated PDT.
Photodynamic therapy with fullerenes in vivo : reality or a dream?
Nanomedicine, 2011
Photodynamic therapy (PDT) employs the combination of nontoxic photosensitizers and visible light that is absorbed by the chromophore to produce long-lived triplet states that can carry out photochemistry in the presence of oxygen to kill cells. The closed carbon-cage structure found in fullerenes can act as a photosensitizer, especially when functionalized to impart water solubility. Although there are reports of the use of fullerenes to carry out light-mediated destruction of viruses, microorganisms and cancer cells in vitro, the use of fullerenes to mediate PDT of diseases such as cancer and infections in animal models is less well developed. It has recently been shown that fullerene PDT can be used to save the life of mice with wounds infected with pathogenic Gram-negative bacteria. Fullerene PDT has also been used to treat mouse models of various cancers including disseminated metastatic cancer in the peritoneal cavity. In vivo PDT with fullerenes represents a new application in nanomedicine.
Biomedical potential of the reactive oxygen species generation and quenching by fullerenes (C 60
Biomaterials, 2008
Fullerene (C 60 ), a third carbon allotrope, is a classical engineered material with the potential application in biomedicine. One of the biologically most relevant features of C 60 is the ability to quench various free radicals, behaving as a ''free radical sponge''. Conversely, photosensitization of C 60 leads to its transition to a long-lived triplet excited state and the subsequent energy or electron transfer to molecular oxygen, yielding highly reactive singlet oxygen ( 1 O 2 ) or superoxide anion (O 2 À ), respectively. These reactive oxygen species (ROS) react with a wide range of biological targets and are known to be involved in both cellular signaling and cell damage. Therefore, the dual property of fullerenes to either quench or generate cell-damaging ROS could be potentially exploited for their development as cytoprotective or cytotoxic anticancer/antimicrobial agents. However, the attempts to that effect have been hampered by the extremely low water solubility of C 60 , and by the fact that solubilization procedures profoundly influence the ROS-generating/quenching properties of C 60 , either through chemical modification or through formation of complex nanoscale particles with different photophysical properties. We here analyze the mechanisms and biological consequences of ROS generation/quenching by C 60 , focusing on the influence that different physico-chemical alterations exert on its ROS-related biological behavior.
Biomaterials, 2009
We demonstrated that three different types of water-soluble fullerenes materials can intercept all of the major physiologically relevant ROS. C 60 (C(COOH) 2 ) 2 , C 60 (OH) 22 , and Gd@C 82 (OH) 22 can protect cells against H 2 O 2 -induced oxidative damage, stabilize the mitochondrial membrane potential and reduce intracellular ROS production with the following relative potencies: Gd@C 82 (OH) 22 ! C 60 (OH) 22 > C 60 (C(COOH) 2 ) 2 . Consistent with their cytoprotective abilities, these derivatives can scavenge the stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH), and the reactive oxygen species (ROS) superoxide radical anion (O 2 À ), singlet oxygen, and hydroxyl radical (HO ), and can also efficiently inhibit lipid peroxidation in vitro. The observed differences in free radical-scavenging capabilities support the hypothesis that both chemical properties, such as surface chemistry induced differences in electron affinity, and physical properties, such as degree of aggregation, influence the biological and biomedical activities of functionalized fullerenes. This represents the first report that different types of fullerene derivatives can scavenge all physiologically relevant ROS. The role of oxidative stress and damage in the etiology and progression of many diseases suggests that these fullerene derivatives may be valuable in vivo cytoprotective and therapeutic agents.
ECS transactions, 2013
Photodynamic inactivation of pathogenic bacteria and cancer cells by novel water-soluble decacationic fullerene monoadducts, C60[>M(C3N6 (+)C3)2] and C70[>M(C3N6 (+)C3)2], were investigated. In the presence of a high number of electron-donating iodide anions as parts of quaternary ammonium salts in the arm region, we found that C70[>M(C3N6 (+)C3)2] produced more highly reactive HO(•) radical than C60[>M(C3N6 (+)C3)2], in addition to singlet oxygen ((1)O2). This finding offers an explanation of the preferential killing of Gram-positive and Gram-negative bacteria by C60[>M(C3N6 (+)C3)2] and C70[>M(C3N6 (+)C3)2], respectively. The hypothesis is that (1)O2 can diffuse more easily into porous cell walls of Gram-positive bacteria to reach sensitive sites, while the less permeable Gram-negative bacterial cell wall needs the more reactive HO(•) to cause real damage.
A Bio‐Conjugated Fullerene as a Subcellular‐Targeted and Multifaceted Phototheranostic Agent
Advanced Functional Materials, 2021
Fullerenes are candidates for theranostic applications because of their high photodynamic activity and intrinsic multimodal imaging contrast. However, fullerenes suffer from low solubility in aqueous media, poor biocompatibility, cell toxicity, and a tendency to aggregate. C 70 @lysozyme is introduced herein as a novel bioconjugate that is harmless to a cellular environment, yet is also photoactive and has excellent optical and optoacoustic contrast for tracking cellular uptake and intracellular localization. The formation, water-solubility, photoactivity, and unperturbed structure of C 70 @lysozyme are confirmed using UV-visible and 2D 1 H, 15 N NMR spectroscopy. The excellent imaging contrast of C 70 @lysozyme in optoacoustic and third harmonic generation microscopy is exploited to monitor its uptake in HeLa cells and lysosomal trafficking. Last, the photoactivity of C 70 @lysozyme and its ability to initiate cell death by means of singlet oxygen (1 O 2) production upon exposure to low levels of white light irradiation is demonstrated. This study introduces C 70 @lysozyme and other fullerene-protein conjugates as potential candidates for theranostic applications.
Fullerenes for the treatment of cancer: an emerging tool
Environmental Science and Pollution Research
Cancer is a most common cause of mortality globally. Available medicines possess severe side effects owing to their non-specific targeting. Hence, there is a need of an alternative in the healthcare system that should have high efficacy with the least side effects, also having the ability to achieve site-specific targeting and be reproducible. This is possible with the help of fullerenes. Fullerenes are having the unique physicochemical and photosensitizer properties. This article discusses the synthesis, functionalization, mechanism, various properties, and applications of C60 fullerenes in the treatment of cancer. The review article also addresses the various factors influencing the activity of fullerenes including the environmental conditions, toxicity profile, and future prospective. Graphical abstract