Multimodality labeling of NGR-functionalized hyaluronan for tumor targeting and radiotherapy.

Hyaluronan (HA) is a negatively charged linear polysaccharide that can interact with cluster determinant 44 (CD44) overexpressed cancers. However, HA can also bind to excess substrates in the human body leading to the lower specificity of tumor targeting. Conjugation of other targeting group to HA could enhance the uptake by cancer cell comparing to that of native HA. In this study, we develop the multi-functionalized HA (177Lu-DOTA/Alexa647-HA100-N) for malignant tumor targeting. An asparagine-glycine-arginine (NGR) based peptide was selected for HA functionalization. The peptide is known to target CD13 receptor that is overexpressed in malignant tumors with abundant blood vessels, such as lung cancer. Furthermore, the fluorescent probe Alexa Fluor 647 for ex vivo/in vivo tracking and the radionuclide 177Lu for radioactive therapy were both labeled on the material. The functionalized HA could be bound by lung cancer cells and breast cancer cells. In vivo fluorescent imaging showed that the material could accumulate in the tumor site for more than 96 h. The 177Lu labeling of functionalized HA was stable for more 48 h at physiological conditions. The accumulation of 177Lu-DOTA/Alexa647-HA100-N in the tumor of lung cancer (NCI-H292) bearing mice was 1.91±0.97%ID/g, and it was about 17 times higher than the value in blood. Conclusion: The multimodality labeled functional HA was successfully prepared and could be fluorescent trackable ex vivo and in vivo. It showed high potential to be used for malignant cancer radiotherapy for its specific targeting property to tumors and radiotoxicity from the labeled 177Lu radionuclide.

Evaluating the Photodynamic Biocidal Activity and Investigating the Mechanism of Thiazolium Cyanine Dyes.

In order to develop ideal photosensitizers for photodynamic therapy (PDT), a thiazolium group was introduced in cyanine dyes to possess the advantages of intense absorption in the visible region and anti-microbial activity. We evaluated the anti-bacterial activity of the three thiazolium cyanine dyes against Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria) in vitro. This is the first time that such kinds of cyanine dyes are applied in the photodynamic antibiotic area. Cyanines display excellent anti-bacterial activity to S. aureus and E. coli exposed to white light irradiation, and the corresponding light-induced biocidal efficacy of cyanines increased with irradiation time and concentration. At the same time, there was no observation of dark anti-bacterial abilities. Especially, cyanines show low cell cytotoxicity and excellent biocompatibility. These results suggest that thiazolium cyanine could work as a photosensitizer in PDT with great promise and broad applications for killing bacteria. Mechanistic studies suggest that the reactive oxygen species (ROS) is the vital factor for combating bacteria exposure to white light conditions, whereas it is not the only determining factor of the biocidal activity. The interaction of the cyanine to the cell membrane also plays a critical role in killing bacteria, which has exhibited a synergic effect of electrostatic and hydrophobic interactions. It influences the cell uptake and the membrane perturbation activity of the cyanines, which indirectly affects the biocidal activity.