A new trick (hydroxyl radical generation) of an old vitamin (B2) for near-infrared-triggered photodynamic therapy

Abstract

The photosensitizer has been supposed to be the key component in photodynamic therapy (PDT). Natural products and their intricate molecular frameworks are often used as starting points for drug discovery. Riboflavin (RF), also known as vitamin B₂, has a unique conjugate structure of an isoalloxazine ring, and is a potential photosensitizer for use in the PDT of cancers. In this study, a novel near-infrared (NIR) mediated nanocomposite for PDT is presented, using this old vitamin (RF) as a PDT photosensitizer, integrated with the upconversion nanotechnology. Mesoporous silica coated sodium yttrium fluoride:ytterbium/thulium (NaYF₄:Yb/Tm) nanoparticles were fabricated and used as drug carriers and photo-transducers. Chemical modification of RF was performed to obtain a photostable photosensitizer, 2′,3′,4′,5′-tetraacetylriboflavin (RTA). There is a good overlap between the fluorescence emission of NaYF₄:Yb/Tm nanoparticles and the UV-visible absorption of RTA. The RTA molecules were incorporated into the mesoporous silica shell and the fluorescent emission from the NaYF₄:Yb/Tm nanoparticles can be absorbed by RTA molecules under NIR irradiation. NIR-initiated reactive oxygen species generation was validated using electron paramagnetic resonance (EPR) spectroscopy combined with spin trapping. The results from the in vitro cell test show that this nanocomposite has good photodynamic efficacy. All the chemicals involved in this process are non-toxic, environmentally benign, and easily available. Thus, this nanocomposite has great potential in PDT applications.