Organelle-targeted photosensitization represents a promising approach in photodynamic therapy where the design of the active photosensitizer (PS) is very crucial. In this work, we developed a macromolecular PS with multiple copies of mitochondria-targeting groups and ruthenium complexes that displays highest phototoxicity toward several cancerous cell lines. In particular, enhanced anticancer activity was demonstrated in acute myeloid leukemia cell lines, where significant impairment of proliferation and clonogenicity occurs. Finally, attractive two-photon absorbing properties further underlined the great significance of this PS for mitochondria targeted PDT applications in deep tissue cancer therapy.

CuAAC (Cu(i) catalyzed azide-alkyne cycloaddition) click chemistry has emerged as a versatile tool in the development of photoactive ruthenium complexes with multilateral potential applicability. In this contribution we discuss possible synthetic approaches towards CuAAC reactions with ruthenium(ii) polypyridine complexes and their differences with respect to possible applications. We focus on two main application possibilities of the click-coupled ruthenium assemblies. New results within the development of ruthenium based photosensitizers for the field of renewable energy supply, i.e. DSSCs (dye-sensitized solar cells) and artificial photocatalysis for the production of hydrogen, or for anticancer photodynamic therapeutic applications are reviewed.

Bromo-functionalized precursor molecules are essential for generating desired target compounds through crosscoupling reactions. Herein we show an improved synthetic route, feasible at low temperatures and affording high yields, to the ligands 5-bromo-1,10-phenanthroline (1) and 5,6-dibromo-1,10-phenanthroline (2). The corresponding ruthenium complexes, containing various equivalents of ligand 2, are easily accessible in high yields, including the analogue of tris-homoleptic [Ru(bpy) 3 ] 2+ (bpy = 2,2′-bipyridine), [Ru (2) 3 ] 2+ . X-ray dif- [a]

This contribution describest he excited-state properties of an Osmium-complex when taken up into human cells. The complex 1 [Os(bpy) 2 (IP-4T)](PF 6) 2 with bpy = 2,2'-bipyridine and IP-4T = 2-{5'-[3',4'-diethyl-(2,2'-bithien-5-yl)]-3,4-diethyl-2,2'-bithiophene}imidazo[4,5-f] [1,10]phenanthroline) can be discussed as ac andidate for photodynamic therapy in the biological red/NIR window. The complex is takenu pb yMCF7 cells andl ocalizes rather homogeneously within in the cytoplasm. To detail the sub-ns photophysics of 1,c omparativet ransienta bsorptionm easurements were carried out in different solvents to derive am odel of the photoinduced processes. Key to rationalize the excited-state relaxationis al onglived 3 ILCT state associated with the oligothiophene chain. This model was then tested with the complex internalized into MCF7 cells, since the intracellular environment has long been suspected to take big influence on the excited state properties. In our study of 1 in cells, we were able to show that, though the overallm odel remained the same, the excited-state dynamics are affectedstrongly by the intracellular environment. Our study represents the first in depth correlation towards ex-vivo and in vivo ultrafast spectroscopy for apossible photodrug.

Acute myeloid leukemia (AML) is characterized by relapse and treatment resistance in a major fraction of patients, underlining the need of innovative AML targeting therapies. Here we analysed the therapeutic potential of an innovative biohybrid consisting of the tumor-associated peptide somatostatin and the photosensitizer ruthenium in AML cell lines and primary AML patient samples. Selective toxicity was analyzed by using CD34 enriched cord blood cells as control. Treatment of OCI AML3, HL60 and THP1 resulted in a 92, and 99 and 97% decrease in clonogenic growth compared to the controls. Primary AML cells demonstrated a major response with a 74 to 99% reduction in clonogenicity in 5 of 6 patient samples. In contrast, treatment of CD34 + cB cells resulted in substantially less reduction in colony numbers. Subcellular localization assays of RU-SST in OCI-AML3 cells confirmed strong co-localization of RU-SSt in the lysosomes compared to the other cellular organelles. our data demonstrate that conjugation of a Ruthenium complex with somatostatin is efficiently eradicating LSc candidates of patients with AML. this indicates that receptor mediated lysosomal accumulation of photodynamic metal complexes is a highly attractive approach for targeting AML cells. Acute myeloid leukemia (AML) is initiated and propagated by cancer stem cells. Although these leukemic stem cells (LSCs) initially respond to chemotherapy, most patients relapse and die from the disease 1. One explanation is that current therapies only eliminate the tumor bulk which lacks leukemic stem cell properties whereas the LSCs are relatively insensitive. Growing knowledge of the molecular landscape of AML has led to clinical testing of new drugs against driver mutations as well as antibody-based therapies against cell surface proteins with partly disappointing results 2-5. Thus, for the majority of patients there is therapeutic standstill and the urgent need for innovative treatment approaches. Tumor-associated peptides provide attractive characteristics for AML-targeted strategies such as easy availability, convenient purification and storage. In addition, they are less immunogenic, have a high tissue penetration and a high affinity to cellular biomarkers. They provide a rapid clearance from the body and are excellent candidates for straight forward conjugation strategies. It has been shown that somatostatin receptors (SSTR) are expressed on leukemias such as T-cell leukemia and AML 6,7. Using a somatostatin radiobinding assay it was demonstrated that around 12.5% of AML cases express somatostatin receptors 6. Previously, it has been shown that primary AML progenitor cells, characterized by the co-expression of CD34 and CD117 express the somatostatin receptor (SSTR) subtype 2 and that the expression of the SSTR2 receptor was not restricted to the immature CD34 + CD117 + compartment, but also detected on more differentiated AML blasts. Using a transwell migration assay, it was demonstrated that the migration of AML cells towards a gradient