Proton-dynamic therapy following photosensitiser activation by accelerated protons demonstrated through fluorescence and singlet oxygen production.

We demonstrate excitation of photosensitisers (PSs) by accelerated protons to produce fluorescence and singlet oxygen. Their fluorescence follows a pattern similar to the proton energy loss in matter, while proton-derived fluorescence spectra match the photon-induced spectra. PSs excited in dry gelatin exhibit enhanced phosphorescence, suggesting an efficient PSs triplet state population. Singlet oxygen measurements, both optically at ~1270 nm and through the photoproduct of protoporphyrin IX (PpIX), demonstrate cytotoxic singlet oxygen generation by proton excitation. The singlet oxygen-specific scavenger 1,4-diazabicyclo[2.2.2]octane (DABCO) abrogates the photoproduct formation under proton excitation, but cannot countermand the overall loss of PpIX fluorescence. Furthermore, in two cell lines, M059K and T98G, we observe differential cell death upon the addition of the PS cercosporin, while in U87 cells we see no effect at any proton irradiation dose. Our results pave the way for a novel treatment combining proton therapy and "proton-dynamic therapy" for more efficient tumour eradication.

Guanidinylated dendritic molecular transporters: prospective drug delivery systems and application in cell transfection.

In the present review the crucial role of the guanidinium functional group in facilitating the transport of dendritic polymers through liposomal and cell membranes is discussed, along with other structural features of guanidinylated dendritic polymers that fine-tune their transport properties, and even determine their subcellular destinations. In this context, an ideal dendritic molecular transporter would need to possess a dendritic scaffold of the appropriate size and degree of guanidinylation, flexibility of the guanidinium moiety, and should exhibit a proper balance between hydrophilic and hydrophobic moieties located on the dendritic surface. All of the above are illustrated through selected paradigms from the relevant literature, which give a valuable insight into forging successful dendritic delivery systems for both drugs and genes. The main challenge for the future focus of the field is identified as the determination of the key structural and functional characteristics that will enhance cell internalisation, and secure localisation in specific subcellular organelles.