Functionalizing Collagen with Vessel-Penetrating Two-Photon Phosphorescence Probes: A New In Vivo Strategy to Map Oxygen Concentration in Tumor Microenvironment and Tissue Ischemia.

The encapsulation and/or surface modification can stabilize and protect the phosphorescence bio-probes but impede their intravenous delivery across biological barriers. Here, a new class of biocompatible rhenium (ReI ) diimine carbonyl complexes is developed, which can efficaciously permeate normal vessel walls and then functionalize the extravascular collagen matrixes as in situ oxygen sensor. Without protective agents, ReI -diimine complex already exhibits excellent emission yield (34%, λem   = 583 nm) and large two-photon absorption cross-sections (σ2   = 300 GM @ 800 nm) in water (pH 7.4). After extravasation, remarkably, the collagen-bound probes further enhanced their excitation efficiency by increasing the deoxygenated lifetime from 4.0 to 7.5 µs, paving a way to visualize tumor hypoxia and tissue ischemia in vivo. The post-extravasation functionalization of extracellular matrixes demonstrates a new methodology for biomaterial-empowered phosphorescence sensing and imaging.

Water-soluble cyclometalated platinum(ii) and iridium(iii) complexes: synthesis, tuning of the photophysical properties, and in vitro and in vivo phosphorescence lifetime imaging.

This paper presents synthesis and photophysical investigation of cyclometalated water-soluble Pt(ii) and Ir(iii) complexes containing auxiliary sulfonated diphosphine (bis(diphenylphosphino)benzene (dppb), P^P*) ligand. The complexes demonstrate considerable variations in excitation (extending up to 450 nm) and emission bands (with maxima ranging from ca. 450 to ca. 650 nm), as well as in the sensitivity of excited state lifetimes to molecular oxygen (from almost negligible to more than 4-fold increase in degassed solution). Moreover, all the complexes possess high two-photon absorption cross sections (400-500 GM for Pt complexes, and 600-700 GM for Ir complexes). Despite their negative net charge, all the complexes demonstrate good uptake by HeLa cells and low cytotoxicity within the concentration and time ranges suitable for two-photon phosphorescence lifetime (PLIM) microscopy. The most promising complex, [(ppy)2Ir(sulfo-dppb)] (Ir1*), upon incubation in HeLa cells demonstrates two-fold lifetime variations under normal and nitrogen atmosphere, correspondingly. Moreover, its in vivo evaluation in athymic nude mice bearing HeLa tumors did not reveal acute toxicity upon both intravenous and topical injections. Finally, Ir1* demonstrated statistically significant difference in lifetimes between normal tissue (muscle) and tumor in macroscopic in vivo PLIM imaging.

Infrared-active quadruple contrast FePt nanoparticles for multiple scale molecular imaging.

A single nanomaterial with multiple imaging contrasts and functions is highly desired for multiscale theragnosis. Herein, we demonstrate single 1-1.9 µm infrared-active FePt alloy nanoparticles (FePt NPs) offering unprecedented four-contrast-in-one molecular imaging - computed tomography (CT), magnetic resonance imaging (MRI), photoacoustic (PA) imaging, and high-order multiphoton luminescence (HOMPL) microscopy. The PA response of FePt NPs outperforms that of infrared-active gold nanorods by 3- to 5.6-fold under identical excitation fluence and particle concentrations. HOMPL (680 nm) of an isolated FePt NP renders spatial full-width-at-half-maximum values of 432 nm and 300 nm beyond the optical diffraction limit for 1230-nm and 920-nm excitation, respectively. The in vivo targeting function was successfully visualized using HOMPL, PA imaging, CT, and MRI, thereby validating FePt as a single nanomaterial system covering up to four types (Optical/PA/CT/MRI) of molecular imaging contrast, ranging from the microscopic level to whole-body scale investigation.