Synergy and translation of allogenic bone marrow stem cells after photodynamic treatment of rheumatoid arthritis with tetra sulfonatophenyl porphyrin and TiO2 nanowhiskers

Rheumatoid arthritis （RA） etiology and amelioration remains a challenge in modern therapeutics. Herein, we explored the synergistic effect of allogenic bone marrow stem cell （BMSC） translation and photodynamic treatment of RA with tetra sulfonatophenyl porphyrin （TSPP） and TiO2 nanocomposites as a new strategy for RA theranostics. The translation of BMSCs with miRNAs into infected joints in long bones post-photodynamic therapy is helpful for treating and understanding RA pathophysiology. We observed that allogenic BMSC translation combined with TSPP-TiO2 nanocomposites can significantly （p 〈 0.01） lower the concentrations of serum biomarkers （tumor necrosis factor-α and interleukin-17） in a collagen induced arthritis （CIA） murine model, both in vitro and in vivo, as well as improve other parameters such as arthritis score, BMSC count, complete blood count, and numbers of platelets, red blood cells, and white blood cells. Moreover, a fluorescent TSPP in the feet or long bones and X-ray bioimaging of RA joints revealed the clinical efficacy of BMSCs combined with TSPP-TiO2 nanocomposites. Microarray data analysis illustrated that rnomir-375-3p and rno-mir-196b-3p were up-regulated by approximately 100-fold in the BMSCs of ameliorated RA post-photodynamic therapy with TSPP-TiO2 nanocomposites. Our study not only suggests a new approach for RA theranostics, but also helps in understanding RA pathophysiology.

Rapid and multimodal in vivo bioimaging of cancer cells through in situ biosynthesis of Zn＆Fe nanoclusters

Early diagnosis remains highly important for efficient cancer treatment, and hence, there is significant interest in the development of effective imaging strategies. This work reports a new multimodal bioimaging method for accurate and rapid diagnosis of cancer cells by introducing aqueous Fe^2＋ and Zn^2＋ ions into cancer cells （i.e., HeLa, U87, and HepG2 cancer cells）. We found that the biocompatible metal ions Fe^2＋ and Zn^2＋ forced the cancer cells to spontaneously synthesize fluorescent ZnO nanoclusters and magnetic Fe3O4 nanoclusters. These clusters could then be used for multimodal cancer imaging by combining fluorescence imaging with magnetic resonance imaging and computed tomography imaging. Meanwhile, for normal cells （i.e., L02） and tissues, neither fluorescence nor any other obvious difference could be detected between pre- and post-injection. This multimodal bioimaging strategy based on the in situ biosynthesized Zn＆Fe oxide nanoclusters might therefore be useful for early cancer diagnosis and therapy.

Titanium dioxide-tetra sulphonatophenyl porphyrin nanocomposites for target cellular bio-imaging and treatment of rheumatoid arthritis

Photodynamic therapy(PDT) is one of the latest biomedical technologies used for treatment of various neoplastic and non-neoplastic diseases. However, there still exist some well-known problems regarding its efficacy, e.g. effective concentration of the drug at the desired sites, the irradiation light dosimetry and biocompatibility of the photosensitizer. The introduction of nanotechnology and nanomaterial like biocompatible nano-titania(i.e., nano-TiO_2) may facilitate to solve some of these problems. In this study we have explored the possibility of combining tetra sulphonatophenyl porphyrin(TSPP) with nano-titania(PT) for efficient PDT with least adverse effects. The spectroscopic properties of these nano-composites were characterized by using fluorescence and UV-Vis absorption spectroscopic study. The singlet oxygen quantum yield was determined by using 2,5-diphenyl-3,4-benzofuran(DPBF), while the effect of nano TiO_2 with TSPP on the synovial fibroblast cells from human(HSC) and rat models(RSC) were investigated by confocal laser microscopy and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. Our results suggest that nano TiO_2 with TSPP can be readily utilized for effective PDT treatment of Rheumatoid Arthritis(RA).