Progress and Perspective of Solid-State Organic Fluorophores for Biomedical Applications.

Fluorescent organic dyes have been extensively used as raw materials for the development of versatile imaging tools in the field of biomedicine. Particularly, the development of solid-state organic fluorophores (SSOFs) in the past 20 years has exhibited an upward trend. In recent years, studies on SSOFs have focused on the development of advanced tools, such as optical contrast agents and phototherapy agents, for biomedical applications. However, the practical application of these tools has been hindered owing to several limitations. Thus, in this Perspective, we have provided insights that could aid researchers to further develop these tools and overcome the limitations such as limited aqueous dispersibility, low biocompatibility, and uncontrolled emission. First, we described the inherent photophysical properties and fluorescence mechanisms of conventional, aggregation-induced emissive, and precipitating SSOFs with respect to their biomedical applications. Subsequently, we highlighted the recent development of functionalized SSOFs for bioimaging, biosensing, and theranostics. Finally, we elucidated the potential prospects and limitations of current SSOF-based tools associated with biomedical applications.

A two-photon fluorescence self-reporting black phosphorus nanoprobe for the in situ monitoring of therapy response.

The in situ and real-time supervision of reactive oxygen species (ROS) generated during photodynamic therapy (PDT) is of great significance for lessening nonspecific damage and guiding personalized therapy. However, photosensitizers frequently fail to deliver successful treatment accompanying the ROS-related imaging signals produced, impeding simple treatment outcome predictions and therapeutic schedule adjustments. Here, we report a two-photon fluorescence self-reporting strategy for the in situ and real-time monitoring of treatment response via a novel black phosphorus-based two-photon nanoprobe (TPBP). TPBP effectively generated singlet oxygen (1O2) under near-infrared laser irradiation for PDT, and 1O2 stimulated a two-photon molecule to emit fluorescence signals for feedback of 1O2 generation, which facilitated the regulation of treatment parameters to achieve precise and personalized medicine in deep tissue.

Oxygen-Embedded Quinoidal Acene Based Semiconducting Chromophore Nanoprobe for Amplified Photoacoustic Imaging and Photothermal Therapy.

Photoacoustic (PA) imaging as a noninvasive biomedical imaging technology exhibits high spatial resolution and deep tissue penetration for in vivo imaging. In order to fully explore the potential of PA imaging in biomedical applications, new contrast agents with improved PA stability and efficiency are in high demand. Herein, we present a new PA agent based on an oxygen-embedded quinoidal nonacene chromophore that is self-assembled into nanoparticles (Nano(O-Nonacene)-PEG), assisted by polyethylene glycol (PEG). Notably, the photothermal conversion efficiency of Nano(O-Nonacene)-PEG is 1.5 fold that of semiconducting polymer nanoparticles (Nano(PCPDTBT)-PEG) and 2.8 fold that of Au nanorods, owing to the low quantum yield of Nano(O-Nonacene)-PEG. Thereby, Nano(O-Nonacene)-PEG possess a greatly elevated PA signal intensity, compared to Nano(PCPDTBT)-PEG and Au nanorods, which have been widely explored for PA imaging. Due to the high resistance to photo bleaching, Nano(O-Nonacene)-PEG exhibits higher PA signal stability, which may be employed for long-term PA imaging. Moreover, when magnetic Zn0.4Fe2.6O4 nanoparticles are incorporated into Nano(O-Nonacene)-PEG, not only are magnetic resonance signals generated but also the photoacoustic efficacy is greatly enhanced. Therefore, Nano(O-Nonacene)-PEG offers distinct properties: (i) the elevated photoacoustic effect allows for high-resolution photoacoustic imaging, (ii) small size (10 nm in diameter) results in efficient tumor-targeting, and (iii) the facile application of efficient photothermal therapy in vivo. The current work offers the possibility of oxygen-embedded quinoidal acene as a promising PA probe for precision phototheranostics.

Nitric Oxide-Activated "Dual-Key-One-Lock" Nanoprobe for in Vivo Molecular Imaging and High-Specificity Cancer Therapy.

Cancer treatments are confounded by severe toxic effects toward patients. To address these issues, activatable nanoprobes have been designed for specific imaging and destruction of cancer cells under the stimulation of specific cancer-associated biomarkers. Most activatable nanoprobes were usually activated by some single-factor stimulation, but this restricts therapeutic specificity between diseased and normal tissue; therefore, multifactor activation is highly desired. To this end, we herein develop a novel dual-stimuli responsive theranostic nanoprobe for simultaneously activatable cancer imaging and photothermal therapy under the coactivation of "dual-key" stimulation of "nitric oxide (NO)/acidity", so as to further improve the therapeutic specificity. Specifically, we have integrated a weak electron acceptor (benzo[c][1,2,5]thiadiazole-5,6-diamine) into a donor-π-acceptor-π-donor type chromophore. When the weak acceptor was oxidized by NO in acidic conditions to form a stronger acceptor (5H-[1,2,3]triazolo[4,5-f]-2,1,3-benzothiadiazole), the molecule absorption was significantly increased in the near-infrared region, based on the intramolecular charge transfer (ICT) mechanism. Under the dual-key stimulation of NO/acidity within the tumor associated with inflammation, the nanoprobe can correspondingly output dual signals for ratiometric photoacoustic and photothermal imaging of cancer in vivo and do so with enhanced accuracy and specificity. Our novel nanoprobe exhibited higher photoacoustic signal enhancement under dual-factor activation at 9.8 times that of NO and 132 times that of acidity alone, respectively. Moreover, through such dual activation of NO/acidity, the nanoprobe produces more differentiation of hyperthermia between tumor and normal tissues, to afford satisfactory photothermal therapy with minimal toxic side effects. Thus, our work presents a promising strategy for significantly improving the precision and specificity of cancer imaging and therapy.

Construction of an efficacious model for a nondestructive identification of traditional Chinese medicines Liuwei Dihuang pills from different manufacturers using near-infrared spectroscopy and moving window partial least-squares discriminant analysis.

This paper reports on the construction of an efficacious model for a non-invasive identification of traditional Chinese medicines, Liuwei Dihuang pills from different manufacturers, on the basis of near-infrared spectra (NIRS) coupled with moving window partial least-squares discriminant analysis (MWPLSDA). Considering the continuity of near-infrared spectral measurements, MWPLSDA is used to identify continuous and highly classification-related information intervals, a simple, yet effective classification model that can be developed for identifying accurate 150 Liuwei Dihuang pills from five different manufacturers. Meanwhile, the method is compared with some traditional pattern-recognition methods including principal component analysis (PCA), linear discriminant analysis (LDA) and partial least-squares discriminant analysis (PLSDA). The obtained results show that the method not only can reduce the operation time, but also significantly improves the classification accuracy. Hence, the nondestructive method can be expected to be promising for more practical applications on quality control and the discrimination of traditional Chinese medicine.