NIR‐II J‐Aggregated Pt(II)‐Porphyrin‐Based Phosphorescent Probe for Tumor‐Hypoxia Imaging

Abstract

The luminescence of traditional phosphorescence-based hypoxia probes is limited to the visible and first near-infrared wavelength regions (<1000 nm), which has defects of higher light scattering and lower penetration depth in contrast with the second near-infrared wavelength window (NIR-II, 1000-1700 nm) for optical bioimaging. Herein, 5,15-bis(2,6-bis(dodecyloxy) phenyl)-porphyrin platinum(II) (PpyPt) with J-aggregation induced NIR-II phosphorescence is reported. J-aggregates of PpyPt are confirmed by the X-ray diffraction data in the crystalline state. Moreover, the emission and excitation spectra of PpyPt in the solid states reveal NIR-II luminescence feature of PpyPt in J-aggregates. More importantly, by preparation of water-soluble PpyPt nanoparticles (PpyPt NPs 4.76 ) with J-aggregates, it has NIR-II phosphorescent lifetime of microseconds and good oxygen-sensitivity in water. Moreover, the good biological hypoxia-sensing potential of PpyPt NPs 4.76 is demonstrated in cells and 4T1-tumor-bearing mice. This study provides an efficient strategy to design NIR-II phosphorescent probe for sensitive tumor-hypoxia detection through the construction of J-aggregates.

Enhancing NIR-II Phosphorescence through Phosphorescence Resonance Energy Transfer for Tumor-Hypoxia Imaging

“…As we can see, the NIR-II signals of the two phosphorescent NPs were mainly located at the tumor and reticuloendothelial system (RES) (for example, liver and spleen tissues). Referring to the previous study, 27,34 the bright NIR-II signal in tumor was attributed to the lighting up of the phosphorescence of reagents by tumor hypoxia. Most of the reagents accumulated in RES resulted in strong NIR-II signals in livers or spleen tissues according to the numerous research works.…”

“…A phosphorescent donor (PpyPtBr, namely PD) and a NIR-II fluorescent acceptor (TTQF, namely FA) of the NIR-II PRET system were synthesized with reference to our previous studies. , The specific synthetic procedure was clearly described in Schemes S1–S4 in the Supporting Information. Briefly speaking, PD was synthesized through a normal three-step method.…”

“…23−26 Unfortunately, these NIR-II phosphors were very rarely reported in existing research; especially, organic NIR-II phosphors were further held back by their low NIR-II phosphorescent quantum yield (below 0.1%). 27 Fluorescence resonance energy transfer (FRET) was welldemonstrated to be an efficient strategy in red-shifted emission spectra, enhancing emission intensity and amplifying single oxygen generation. 28−30 In this system, the energy transfer was from the singlet state of donor to the singlet state of acceptor by an ideal spectral overlap of the donor and acceptor.…”

“…In addition, the NIR-II QY of PRET NPs was 27 times higher than the existing organic NIR-II phosphorescent agent (NIR-II QY (PpyPt NPs 4.76 ) = 0.047%) developed by our group. 27 The luminous brightness value of the promising PRET NPs is calculated to be 292.1 M −1 cm −1 (luminous brightness value = fluorescence quantum yield (QY) × extinction coefficient (ε)) in the normoxic atmosphere. After deoxygenation (Figure S9 in the Supporting Information), the NIR-II QY of PRET NPs reached 3.97%, which was also more than 11 times greater than that of PpyPt NPs 4.76 (0.319%).…”

“…In contrast, NIR-II phosphorescence probes as another autofluorescence-free technology did not depend on those endogenous substrates. Moreover, they had been proven to show higher SBR and sensitivity than NIR-II fluorophores for their excellent characters of long luminescence lifetime, large Stokes shift, and oxygen sensitivity. − Unfortunately, these NIR-II phosphors were very rarely reported in existing research; especially, organic NIR-II phosphors were further held back by their low NIR-II phosphorescent quantum yield (below 0.1%) …”