Self‐Assembly of a Monochromophore‐Based Polymer Enables Unprecedented Ratiometric Tracing of Hypoxia

Abstract

Ratiometric optical imaging holds promise for noninvasive visualization of hypoxic microenvironment induced by cancer cells since it can provide real-time and accurate information on cancers from microscopic to macroscopic levels with built-in calibration. [1] To date, a host of works on ratiometric optical imaging of tumor hypoxia rely on bischromophorebased system, which inevitably compromises imaging accuracy and specificity because of the undesirable energy/charge transferring interactions between the internal reference moiety and sensing chromophore (Scheme 1a). [2] At present, the accurate diagnosis of cancer hypoxia via monochromophore-based sensor with ratiometric readout still remains challenging. [3] Nonconventional fluorescent biogenic and synthetic polymers without aromatic structures have recently attracted considerable attention, and their clusteroluminescence mechanism behind this abnormal phenomenon is increasingly deciphered. [4] For instance, Tang and co-workers found that the intra-and inter-chain n→π* interaction of carbonyl groups plays a crucial role during the emission for oligo(maleic anhydride)s (OMAhs) in the aggregated state/condensed phase. [5] Zhang and co-workers also proposed clustering-triggered emission mechanism, namely the clustering of nonconventional chromophores and subsequent electron cloud can overlap with the simultaneous rigidification of conformation in the process of poly(amino acids). [4c] Thus, we examine whether the nonaromatic clusteroluminescence can be utilized as additional internal reference signal to construct a monochromophore-based ratiometric hypoxia nanosensor.With this in mind, we borrowed the nonaromatic clusteroluminescence strategy and developed a monochromophore-based ratiometric hypoxia probe (Pt-TPP-PVP 430 , Scheme 1b,c), which consists of a hydrophobic oxygen-sensitive Pt(II) tetraphenylporphyrin (Pt-TPP) and a hydrophilic backbone poly(N-vinylpyrrolidone) (PVP). Due to its amphiphilic nature, Pt-TPP-PVP 430 can self-assemble into nanoclusters in an aqueous solution, highly preferential to accumulate at tumor site by passive enhanced permeation and retentionThe 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 monochromophorebased 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 ...

Intrinsic Luminescence from Nonaromatic Biomolecules

“…Fluorescence dyes, due to their on‐off nature, are usually the visible and effective probes in many fields, and some researchers also attempted to detect some specific fluorescent quenchers with the intrinsic fluorescence of nonconventional luminophores . For example, accurate Fe 3+ detection should be an urgent requirement for diagnosing many disorders, such as malaria, anemia, and PD.…”

Nano versus Molecular: Optical Imaging Approaches to Detect and Monitor Tumor Hypoxia

“…Wang et al developed a self-assembly system (Pt-TPP-PVP 430 ), where a PVP chain was covalently conjugated to a Pt (II) tetraphenylporphyrin (PtTPP). [182] The amphiphilic nature of the polymer enabled self-assembly of the conjugate into micelle nanostructures (118 nm). The corresponding nanoparticles showed nanoassembly-driven properties inducing fluorescence at 660 nm, likely a resulting from aggregation, as well as phosphorescence at 760 nm.…”

Ultralong Room-Temperature Phosphorescence of Silicon-Based Pure Organic Crystal for Oxygen Sensing

“…Quantitative oxygen detection is of great significance in various fields, e.g. quantifying O 2 levels provides an important parameter for cancer diagnosis; [1][2][3] quantitative oxygen detection in smoke exhaust is advantageous in improving fuel utilization and reducing exhaust emissions; 4,5 accurate detection of oxygen content in the production process is conducive to improving the output and efficiency in synthetic industry. 6,7 Recently, optical methods through phosphorescence quenching for quantitative oxygen detection have attracted much attention due to their high sensitivity, fast response and in-situ measurements.…”