The production of reactive oxygen species (ROS) by ultrasonic activation of nanomaterials has great potential in sonodynamic therapy and sonocatalysis. Herein, we first demonstrate that watersoluble Au 25 (Captril) 18 nanoclusters (NCs) can work as a sonosensitizer to produce singlet oxygen ( 1 O 2 ) under ultrasound irradiation. The ultrasonically mediated 1 O 2 production was also confirmed in other thiolated Au NCs, including those protected by glutathione or 6-aza-2thiothymine (ATT). There are two possible pathways to ultrasonically excite the thiolated Au NCs via microbubble cavitation: (i) sonoluminescence from water and (ii) ROS production (hydroxyl radical) by pyrolysis cleavage of water. We suggest that the sonoluminescence from water could excite the Au NCs to produce 1 O 2 under ultrasonication, when there is a spectral overlap between the sonoluminescence and the absorption of Au NCs to allow energy transfer. The ultrasonic excitation of ATT-Au NCs was confirmed by the observation of sonoluminescence. The Au(I)-SR shell of thiolated Au NCs is responsible for generating the triplet state of thiolated Au NCs to produce 1 O 2 under ultrasonication. As thiolated Au NCs also have photosensitizing capability, it would be used as ROS-based nanomedicine for a sonodynamic and/or photodynamic therapy.

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Antibacterial photodynamic therapy (aPDT) utilizes reactive oxygen species such as singlet oxygen ( 1 O 2 ) and free radicals via photosensitizers, which are light and light-sensitive agents, to reduce bacterial infections. It has been utilized as a treatment for dental diseases in place of antibiotic therapies. However, aPDT does not always cause the desired therapeutic effect due to the instability of organic photosensitizers and the formation of bacterial biofilms. To promote the antibacterial and antibiofilm effects of aPDT, we have proposed a lysozyme (Lys)-gold nanoclusters (Au NCs)/rose bengal (Lys-Au NCs/RB) conjugate as a novel photosensitizer. This conjugate was found to effectively impede the growth of both gram-positive and gram-negative bacteria when exposed to white light-emitting diode (LED) irradiation. The photoexcited Lys-Au NCs/RB showed significantly higher antibacterial activity than photoexcited Lys-Au NCs or RB alone. The synergistic effect is a result of the combination of Lys (an antibacterial protein) and enhanced 1 O 2 generation related to resonance energy transfer (RET) in the Au NCs/RB conjugate. Photoexcited Lys-Au NCs/RB increased the effects of aPDT in a dose- and time-dependent manner. Furthermore, the photoexcited Lys-Au NCs/RB successfully decreased Streptococcus mutans biofilm formation. However, in contrast, it did not have a negative effect on the proliferation, adhesion, or spread of mammalian cells, indicating low cytotoxicity. Lys-Au NCs/RB is a novel photosensitizer with low cytotoxicity that is capable of bacterial inactivation and the suppression of biofilm formation, and could help to improve dental treatments in the future.

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Carbon nanodots can function as photosensitizers that have the ability to generate reactive oxygen species such as singlet oxygen, hydroxy (OH) radicals, and superoxide ions. However, most of these can only be generated upon ultraviolet light excitation.