Recent advances in type I organic photosensitizers for efficient photodynamic therapy for overcoming tumor hypoxia.

Photodynamic therapy (PDT) with an oxygen-dependent character is a noninvasive therapeutic method for cancer treatment. However, its clinical therapeutic effect is greatly restricted by tumor hypoxia. What's more, both PDT-mediated oxygen consumption and microvascular damage aggravate tumor hypoxia, thus, further impeding therapeutic outcomes. Compared to type II PDT with high oxygen dependence and high oxygen consumption, type I PDT with less oxygen consumption exhibits great potential to overcome the vicious hypoxic plight in solid tumors. Type I photosensitizers (PSs) are significantly important for determining the therapeutic efficacy of PDT, which performs an electron transfer photochemical reaction with the surrounding oxygen/substrates to generate highly cytotoxic free radicals such as superoxide radicals (˙O2-) as type I ROS. In particular, the primary precursor (˙O2-) would progressively undergo a superoxide dismutase (SOD)-mediated disproportionation reaction and a Haber-Weiss/Fenton reaction, yielding higher cytotoxic species (˙OH) with better anticancer effects. As a result, developing high-performance type I PSs to treat hypoxic tumors has become more and more important and urgent. Herein, the latest progress of organic type I PSs (such as AIE-active cationic/neutral PSs, cationic/neutral PSs, polymer-based PSs and supramolecular self-assembled PSs) for monotherapy or synergistic therapeutic modalities is summarized. The molecular design principles and strategies (donor-acceptor system, anion-π+ incorporation, polymerization and cationization) are highlighted. Furthermore, the future challenges and prospects of type I PSs in hypoxia-overcoming PDT are proposed.

Recent Advances in Fluorescent Methods for Polyamine Detection and the Polyamine Suppressing Strategy in Tumor Treatment.

The biogenic aliphatic polyamines (spermine, spermidine, and putrescine) are responsible for numerous cell functions, including cell proliferation, the stabilization of nucleic acid conformations, cell division, homeostasis, gene expression, and protein synthesis in living organisms. The change of polyamine concentrations in the urine or blood is usually related to the presence of malignant tumors and is regarded as a biomarker for the early diagnosis of cancer. Therefore, the detection of polyamine levels in physiological fluids can provide valuable information in terms of cancer diagnosis and in monitoring therapeutic effects. In this review, we summarize the recent advances in fluorescent methods for polyamine detection (supramolecular fluorescent sensing systems, fluorescent probes based on the chromophore reaction, fluorescent small molecules, and fluorescent nanoparticles). In addition, tumor polyamine-suppressing strategies (such as polyamine conjugate, polyamine analogs, combinations that target multiple components, spermine-responsive supramolecular chemotherapy, a combination of polyamine consumption and photodynamic therapy, etc.) are highlighted. We hope that this review promotes the development of more efficient polyamine detection methods and provides a comprehensive understanding of polyamine-based tumor suppressor strategies.

Lipid droplet polarity decreases during the pathology of muscle injury as revealed by a polarity sensitive sensor.

Revealing the relationship between lipid droplets (LDs)polarity and disease is indispensable in clinicopathological diagnosis. So far, muscle injury is often ignored as it is not life-threatening as cardiovascular and cerebrovascular diseases, making the exploration of the internal relationship between muscle injury and LDs polarity a gray area. Herein, a fluorescent probe (CCB) with powerful polar-sensitive as well as precise LDs targeting was designed for visualizing the LDs polarity in the pathology of muscle injury. By means of the probe CCB, the identification of cancer cells and the monitoring of LDs polarity changes in dysfunctional cells were successfully realized. Furthermore, the penetration ability of CCB in tissues of mice was tested to verify the applicability of the probe in organisms. Importantly, by CCB, the relationship between muscle damage and LDs polarity was explored, revealing that muscle damage caused a significant decrease in LDs polarity accompanied by a significant increase in fluorescence. Most importantly, it is the first time to reveal the relationship between muscle damage and LDs polarity. Therefore, the probe CCB will be a powerful monitoring platform for diagnosing related diseases caused by abnormal LDs polarity.

Utilizing a Solvatochromic Optical Agent to Monitor the Polarity Changes in Dynamic Liver Injury Progression.

Unraveling the changing rule of endoplasmic reticulum (ER) polarity is of significance for liver injury. However, the rule of the ER polarity changes during the occurrence and progression of liver injury remains a mystery. Toward that, a unique fluorescent probe, ERNT, capable of imaging ER polarity in multiple liver injury models with high accuracy and fidelity was designed herein. In light of its excellent solvatochromism, the ER polarity was determined to be higher in the case of endoplasmic reticulum stress (ERS) induced by tunicamycin and dithiothreitol than that of the normal state at the cell level. Importantly, with the assistance of the PerkinElmer IVIS Spectrum imaging system and the powerful tool of ERNT, our work first revealed that the ER polarity increases with the evolution of liver injuries. Moreover, as a demonstration, ERNT achieved evaluating hepatoprotective drug efficacy by detecting ER polarity, confirming its high clinical application prospect. Thus, our work not only first unravels the rule of ER polarity in dynamic liver injury progression but may also inspire more diagnostic and therapeutic programs for liver diseases shortly.