Dmitriev, RI,Kondrashina, AV,Koren, K,Klimant, I,Zhdanov, AV,Pakan, JMP,McDermott, KW,Papkovsky, DB

2014

January

Biomaterials Science

Small molecule phosphorescent probes for O-2 imaging in 3D tissue models

Validated

WOS: 77 ()

ORGANOTYPIC SLICE CULTURES STEM-CELL BIOLOGY IN-VITRO INTRACELLULAR OXYGEN TUMOR HYPOXIA CANCER-CELLS BLOOD-FLOW NANOPARTICLES PORPHYRIN PEPTIDES

2

853

866

Monitoring of oxygenation is important for physiological experiments investigating the growth, differentiation and function of individual cells in 3D tissue models. Phosphorescence based O-2 sensing and imaging potentially allow this task; however, current probes do not provide the desired bio-distribution and analytical performance. We present several new cell-penetrating phosphorescent conjugates of a Pt(II)-tetrakis(pentafluorophenyl) porphine (PtPFPP) dye produced by click-modification with thiols, and perform their evaluation as O-2 imaging probes for 3D tissue models. The hydrophilic glucose (Pt-Glc) and galactose (Pt-Gal) conjugates demonstrated minimal aggregation and self-quenching in aqueous media, and efficient in-depth staining of different cell types and multi-cellular aggregates at working concentrations <= 10 mu M. The Pt-Glc probe was applied in high-resolution phosphorescence lifetime based O-2 imaging (PLIM) in multi-cellular spheroids of cancer cells (PC12), primary neural cells (neurospheres) and slices of brain tissue, where it showed good analytical performance, minimal effects on cell viability and appropriate responses to O-2 with phosphorescence lifetimes changing from 20 mu s in air-saturated to 57 mu s under deoxygenated conditions. In contrast, mono-and tetra-substituted oligoarginine conjugates of PtPFPP showed marked aggregation and unstable photophysical properties precluding their use as O-2 sensing probes.

10.1039/c3bm60272a