tetraphenylporphine and Hypoxia

The accuracy of traditional bischromophore-based ratiometric probes is always compromised by undesirable energy/charge transferring interactions between the internal reference moiety and the sensing chromophore. In this regard, ratiometric sensing with a monochromophore system is highly desirable. Herein, an unprecedented monochromophore-based ratiometric probe, which consists of a hydrophilic backbone poly(N-vinylpyrrolidone) (PVP) and single chromophore of platinum(II) tetraphenylporphyrin (Pt-TPP) is reported. Combination of the specific assembled clustering-triggered fluorescent emission (oxygen-insensitive) with the original Pt-TPP phosphorescence (oxygen-sensitive) enables successful construction of a monochromophore-based ratiometric nanosensor for directly tracing hypoxia in vivo, along with the preferable facilitation of enhanced permeation and retention effect and long excitation wavelength. The unique ratiometric signals enable the direct observation from normoxic to hypoxic environment in both living A549 cells and a tumor-bearing mice model, providing a significant paradigm of a monochromophore-based dual-emissive system with the specific assembled cluster emission. The work satisfactorily demonstrates a valuable strategy for designing monochromophore-based dual-emissive materials, and validates its utility for in vivo ratiometric biological sensing without the common energy/charge interference in bischromophore-based system.

Topics: Animals; Cell Line, Tumor; Humans; Hydrophobic and Hydrophilic Interactions; Hypoxia; Mice; Neoplasm Transplantation; Neoplasms; Optical Imaging; Platinum Compounds; Polyvinyls; Porphyrins; Pyrrolidines

Polystyrene nanoparticles (PS-NPs) were doped with an oxygen-sensitive near-infrared (NIR)-emissive palladium meso-tetraphenylporphyrin and an inert reference dye which are both excitable at 635 nm. The nanosensors were characterized with special emphasis on fundamental parameters such as absolute photoluminescence quantum yield and fluorescence lifetime. The PS-NPs were employed for ratiometric dual-wavelength and lifetime-based photoluminescent oxygen sensing. They were efficiently taken up by cultured murine alveolar macrophages, yielding a characteristic and reversible change in ratiometric response with decreasing oxygen concentration. This correlated with the cellular hypoxic status verified by analysis of hypoxia inducible factor-1α (HIF-1α) accumulation. In addition, the surface of PS-NPs was functionalized with polyethylene glycol (PEG) and the monoclonal antibody herceptin, and their binding to HER2/neu-overexpressing tumor cells was confirmed in vitro. First experiments with tumor-bearing mouse revealed a distinctive ratiometric response within the tumor upon hypoxic condition induced by animal sacrifice. These results demonstrate the potential of these referenced NIR nanosensors for in vitro and in vivo imaging that present a new generation of optical probes for oncology.

Topics: Animals; Antibodies, Monoclonal, Humanized; Cell Line, Tumor; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Nanoparticles; Neoplasms; Palladium; Polyethylene Glycols; Polystyrenes; Porphyrins; Protein Binding; Receptor, ErbB-2; Spectroscopy, Near-Infrared; Trastuzumab