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Noncancerous diseases include a wide plethora of medical conditions beyond cancer and are a major cause of mortality around the world. Despite progresses in clinical research, many puzzles about these diseases remain unanswered, and new therapies are continuously being sought. The evolution of bio-nanomedicine has enabled huge advancements in biosensing, diagnosis, bioimaging, and therapeutics. The recent development of aggregation-induced emission luminogens (AIEgens) has provided an impetus to the field of molecular bionanomaterials. Following aggregation, AIEgens show strong emission, overcoming the problems associated with the aggregation-caused quenching (ACQ) effect. They also have other unique properties, including low background interferences, high signal-to-noise ratios, photostability, and excellent biocompatibility, along with activatable aggregation-enhanced theranostic effects, which help them achieve excellent therapeutic effects as an one-for-all multimodal theranostic platform. This review provides a comprehensive overview of the overall progresses in AIEgen-based nanoplatforms for the detection, diagnosis, bioimaging, and bioimaging-guided treatment of noncancerous diseases. In addition, it details future perspectives and the potential clinical applications of these AIEgens in noncancerous diseases are also proposed. This review hopes to motivate further interest in this topic and promote ideation for the further exploration of more advanced AIEgens in a broad range of biomedical and clinical applications in patients with noncancerous diseases.

Chemical warfare agents (CWAs) are toxic chemicals that have been intentionally developed for targeted and deadly use on humans. Although intended for military targets, the use of CWAs more often than not results in mass civilian casualties. To prevent further atrocities from occurring during conflicts, a global ban was implemented through the chemical weapons convention, with the aim of eliminating the development, stockpiling, and use of CWAs. Unfortunately, because of their relatively low cost, ease of manufacture and effectiveness on mass populations, CWAs still exist in today's world. CWAs have been used in several recent terrorist-related incidents and conflicts (

Hydrogen sulfide (H2S) in the endoplasmic reticulum of living systems could be imaged using probe ER-Nap-NBD.

A heavy-atom-free photosensitizer (CI) showed strong singlet oxygen generation, efficient photodynamic therapy and fluorescence bioimaging under two-photon excitation.

Neutrophil elastase (NE) plays a key role in chronic inflammation and acute responses to infection and injury. Effective diseases interventions thus call for precise identification of NE to aid clinical application of such diseases. However, the detection process suffers from this interference of structural changes of NE. Herein, we introduce a molecular probe with high biocompatibility to overcome the interference, which was achieved by combining theoretical calculation and experimental that permits highly specific and sensitive detection of NE in cells and in vivo. The upregulated NE accumulation was specifically measured in inflammation by ratiometric photoacoustic and near-infrared fluorescence imaging, and providing a new method for developing more specific fluorogenic probes for other enzymes.

Chemical warfare agents (CWAs) are among the most prominent threats to the human population, our peace, and social stability. Therefore, their detection and quantification are of utmost importance to ensure the security and protection of mankind. In recent years, significant developments have been made in supramolecular chemistry, analytical chemistry, and molecular sensors, which have improved our capability to detect CWAs. Fluorescent and colorimetric chemosensors are attractive tools that allow the selective, sensitive, cheap, portable, and real-time analysis of the potential presence of CWAs, where suitable combinations of selective recognition and transduction can be integrated. In this review, we provide a detailed discussion on recently reported molecular sensors with a specific focus on the sensing of each class of CWAs such as nerve agents, blister agents, blood agents, and other toxicants. We will also discuss the current technology used by military forces, and these discussions will include the type of instrumentation and established protocols. Finally, we will conclude this review with our outlook on the limitations and challenges in the area and summarize the potential of promising avenues for this field.

Cancer immunotherapy has been a revolutionary cancer treatment modality because it can not only eliminate primary tumors but also prevent metastases and recurrent tumors. Immunogenic cell death (ICD) induced by various treatment modalities, including chemotherapy, phototherapy, and radiotherapy, converts dead cancer cells into therapeutic vaccines, eliciting a systemic antigen-specific antitumor. However, the outcome effect of cancer immunotherapy induced by ICD has been limited due to the low accumulation efficiency of ICD inducers in the tumor site and concomitant damage to normal tissues. The boom in smart nanomaterials is conducive to overcoming these hurdles owing to their virtues of good stability, targeted lesion site, high bioavailability, on-demand release, and good biocompatibility. Herein, the design of targeted nanomaterials, various ICD inducers, and the applications of nanomaterials responsive to different stimuli, including pH, enzymes, reactive oxygen species, or dual responses are summarized. Furthermore, the prospect and challenges are briefly outlined to provide reference and inspiration for designing novel smart nanomaterials for immunotherapy induced by ICD.

Increasingly infectious diseases from microbial pathogens (including bacteria and fungi) threaten human health: a situation that has aroused public health concern around the world. Unfortunately, b...

The discovery of a near-infrared (NIR, 650-900 nm) fluorescent chromophore hemicyanine dye with high structural tailorability is of great significance in the field of detection, bioimaging, and medical therapeutic applications. It exhibits many outstanding advantages including absorption and emission in the NIR region, tunable spectral properties, high photostability as well as a large Stokes shift. These properties are superior to those of conventional fluorogens, such as coumarin, fluorescein, naphthalimides, rhodamine, and cyanine. Researchers have made remarkable progress in developing activity-based multifunctional fluorescent probes based on hemicyanine skeletons for monitoring vital biomolecules in living systems through the output of fluorescence/photoacoustic signals, and integration of diagnosis and treatment of diseases using chemotherapy or photothermal/photodynamic therapy or combination therapy. These achievements prompted researchers to develop more smart fluorescent probes using a hemicyanine fluorogen as a template. In this review, we begin by describing the brief history of the discovery of hemicyanine dyes, synthetic approaches, and design strategies for activity-based functional fluorescent probes. Then, many selected hemicyanine-based probes that can detect ions, small biomolecules, overexpressed enzymes and diagnostic reagents for diseases are systematically highlighted. Finally, potential drawbacks and the outlook for future investigation and clinical medicine transformation of hemicyanine-based activatable functional probes are also discussed.

In this article, we report coumarin derivative 1 bearing cyanoacrylamide and ifenprodil moieties as the first reversible fluorescent probe that can monitor GSH near NMDA receptors.

This tutorial review provides an overview of activatable fluorescent probes for in situ imaging of enzymes, including design strategies, sensing mechanisms, and bioapplications.

Phototherapy has been a promising therapeutic modality for pathological tissue due to its spatiotemporal selectivity and non-invasive characteristics. However, as a core component of phototherapy, a single photosensitizer (PS) nanoplatform integrating excellent therapeutic efficiency and minimal side effects remains an urgent but unmet need. Here, we construct a J-aggregated nano-porphyrin termed MTE based on the self-assembly of methyl-pheophorbide a derivative MPa-TEG (MT) and natural polyphenolic compound epigallocatechin gallate (EGCG). Due to the synergistic interaction between similar large π-conjugated structural EGCG and MT, MTE with small and uniform size is obtained by effectively hindering Ostwald ripening of MT. Noteworthily, MTE not only effectively avoids the inadvertent side effects of phototoxicity during transport thank to the ability of reactive oxygen species (ROS) scavenging, but also achieves two-pathway augmented superior phototherapy: (1) enhancing photodynamic therapy (PDT)

A two-photon fluorogenic probe with the untwisted intramolecular charge process which is comparable to commercial fluorophores has been successfully applied in observing hepatic steatosis.

This review presents a robust strategy to design photosensitizers (PSs) for various species. Photodynamic therapy (PDT) is a photochemical-based treatment approach that involves the use of light combined with a light-activated chemical, referred to as a PS. Attractively, PDT is one of the alternatives to conventional cancer treatment due to its noninvasive nature, high cure rates, and low side effects. PSs play an important factor in photoinduced reactive oxygen species (ROS) generation. Although the concept of photosensitizer-based photodynamic therapy has been widely adopted for clinical trials and bioimaging, until now, to our surprise, there has been no relevant review article on rational designs of organic PSs for PDT. Furthermore, most of published review articles in PDT focused on nanomaterials and nanotechnology based on traditional PSs. Therefore, this review aimed at reporting recent strategies to develop innovative organic photosensitizers for enhanced photodynamic therapy, with each example described in detail instead of providing only a general overview, as is typically done in previous reviews of PDT, to provide intuitive, vivid, and specific insights to the readers.

The outline of the review is as follows. In Section 2, the synthesis and regulatory strategies for BODIPY are summarized, and inspiring cutting-edge work in post-functionalization strategies is highlighted. Section 3 gives a brief overview of assembly model of BODIPY. In this section, we introduce BODIPY as a promising building block for the formation of single- and multi-component self-assembled systems, including nanostructures suitable for aqueous environments, thereby showing the great development potential of supramolecular assembly in biomedicine applications. Section 4 describes the frontier progress of BODIPY in biomedical applications. This section reviews examples of the frontiers of biomedical applications of BODIPY-containing smart materials. It mainly involves the application of materials based on BODIPY building blocks and their assemblies in fluorescence bioimaging, PAI, disease treatment including PDT, PTT and immunotherapy. In Section 5, not only the current status of the BODIPY family in the biomedical field but also the challenges worth considering are summarized. At the same time, it also provides insights into the future development prospects of biomedically applicable BODIPY. This article is protected by copyright. All rights reserved.

We report a mitochondria-targeted nitroreductase (NTR)-activated near-infrared fluorescent probe: CS-NO2. Overexpressed NTR in mitochondria was measured with high sensitivity. More importantly, the probe CS-NO2 successfully monitored NTR activity in solid tumors and a hind-limb model of ischemia in mice. This novel finding indicates the promising function of our probe for the diagnosis of solid tumors and hypoxia-associated diseases.

N-Methyl-d-aspartate (NMDA) is an excitotoxic amino acid used to identify a specific subset of glutamate receptors. The activity of NMDA receptors is closely related to the redox level of the biological system. Glutathione (GSH) as an antioxidant plays a key role with regard to modulation of the redox environment. In this work we designed and developed a GSH-specific fluorescent probe with the capability of targeting NMDA receptors, which was composed of a two-photon naphthalimide fluorophore, a GSH-reactive group sulfonamide, and an ifenprodil targeting group for the NMDA receptor. This probe exhibited high selectivity toward GSH in comparison to other similar amino acids. Two-photon fluorescence microscopy allowed this probe to successfully monitor GSH in neuronal cells and hippocampal tissues with an excitation at 750 nm. It could serve as a potential practical imaging tool to explore the function of GSH and related biological processes in the brain.

Meso-phosphino-substituted BODIPY probes were developed for concise and rapid detection of hypochlorite (ClO-). Interestingly, the probe BP gave a turn-on fluorescence response by shutting the photoinduced electron transfer (PET) effect and extending the coplanar conjugated π-system. In contrast, the probe TMBP showed a colorimetric response toward ClO-. The key role of the steric repulsions was revealed to be for altering the electronic distribution of the BODIPY core, resulting in these obviously different responses. Finally, the probe BP, with high selectivity and sensitivity toward ClO- (LOD = 1.9 nM; response time

Currently, the role of the lysosome, endoplasmic reticulum, or dictyosome in the transcription and translation of programmed cell death ligand 1 (PD-L1) is well revealed, but the role and function of mitochondria in the PD-L1 expression in tumors is still not fully researched, making it hard to offer a novel PD-L1 regulation strategy. In this research, it is newly revealed that mitochondria oxidative phosphorylation (OXPHOS) depression can be used as an effective PD-L1 down-regulation method. To offer an ideal and high-effective tumor mitochondria-targeted OXPHOS depression nanosystem, IR-LND is prepared by conjugating mitochondria-targeted heptamethine cyanine dye IR-68 with mitochondrial complexes I and II depression agent lonidamine (LND), which then further self-assembled with albumin (Alb) to form IR-LND@Alb nanoparticles. By doing this, PD-L1 expression in tumors is selectively and effectively depressed by IR-LND@Alb nanoparticles. As expected, the anti-tumor efficacy of such a PD-L1 depression strategy is superior to conventional anti-PD-L1 monoclonal antibodies. Interestingly, IR-LND can also be served as a novel ideal promising photodynamic therapy (PDT) drug with self-oxygen and self-PD-L1 regulation capacity. All in all, this tumor-selective metabolic reprogramming platform to reactivate immunotherapy and sensitize for PDT effect, would open a new window for mitochondrial immunotherapy for cancer patients.

Bacterial infections can threaten human health. Drug-resistant bacteria have become a challenge because of the excessive use of drugs. We summarize the current metallic antibacterial materials, especially Fe-based materials, for efficiently killing bacteria. The possible antibacterial mechanisms of metallic antibacterial agents are classified into interactions with bacterial proteins, iron metabolism, catalytic activity, and combinations of magnetic, photodynamic, and photothermal effects. This review will inspire the development of novel Fe-based antibacterial agents for clinical settings.

Theranostic, which integrates the diagnosis and tumor treatment in tandem, is an emerging strategy in cancer treatment. Here, we report a novel and unique theranostic nanoparticle, HBCP NP, based on hexa-BODIPY cyclophosphazene (HBCP). Due to the unique bulky molecular structure of HBCP, this nanoparticle can simultaneously perform near-infrared (NIR) fluorescence imaging and photoacoustic imaging (PAI). Interestingly, since reactive oxygen species (ROS) generation of HBCP NPs is completely inhibited, 'safe' fluorescence imaging is possible without the risk of cell damage even under laser irradiation. Finally, NIR fluorescence imaging and PAI in 4T1 tumor-bearing mice demonstrated selective accumulation of HBCP NPs at tumor sites. In addition, HBCP NPs exhibited excellent photothermal effects under high-power laser irradiation, achieving effective tumor growth inhibition.

Adenosine 5'-triphosphate (ATP), synthesized in mitochondria, is an energy molecule in all living things. ATP not only serves as an energy source for protein synthesis and muscle contraction, but also as an important indicator for various diseases, such as Parkinson's disease, cardiovascular disease, and others. Accordingly, detection and sensing of ATP, especially in mitochondria, are important. In this study, a unique ring-opening process of rhodamine was coupled to recognition of ATP via introduction of a thiourea moiety, which was further linked to a naphthalimide group. A strong fluorescent emission at ∼580 nm was accompanied by a color change from colorless to pink upon addition of ATP at pH 7.4. Fluorescent probe 1 successfully imaged mitochondrial ATP with a Pearson's coefficient of 0.8. In addition, green emission from the naphthalimide moiety at ∼530 nm was observed without any change upon addition of ATP. This emission can be considered equivalent to an internal standard to utilize probe 1 as a dual-channel probe for ATP. Furthermore, probe 1 showed negligible cytotoxicity based on MTT assays.