In this review we intend to provide a relatively comprehensive summary of the work of supramolecular hydrogelators after 2004 and to put emphasis particularly on the applications of supramolecular hydrogels/hydrogelators as molecular biomaterials. After a brief introduction of methods for generating supramolecular hydrogels, we discuss supramolecular hydrogelators on the basis of their categories, such as small organic molecules, coordination complexes, peptides, nucleobases, and saccharides. Following molecular design, we focus on various potential applications of supramolecular hydrogels as molecular biomaterials, classified by their applications in cell cultures, tissue engineering, cell behavior, imaging, and unique applications of hydrogelators. Particularly, we discuss the applications of supramolecular hydrogelators after they form supramolecular assemblies but prior to reaching the critical gelation concentration because this subject is less explored but may hold equally great promise for helping ...

Supramolecular Hydrogelators and Hydrogels: From Soft Matter to Molecular Biomaterials

Hydrogels for biomedical applications.

Biophotonics as a highly interdisciplinary frontier often requires the assistance of optical agents to control the light pathways in cells, tissues and living organisms for specific biomedical applications. Organic semiconducting materials (OSMs) composed of π-conjugated building blocks as the optically active components have recently emerged as a promising category of biophotonic agents. OSMs possess common features including excellent optical properties, good photostability and biologically benign composition. This review summarizes the recent progress in the development of OSMs based on small-molecule fluorophores, aggregation-induced emission (AIE) dyes and semiconducting oligomer/polymer nanoparticles (SONs/SPNs) for advanced biophotonic applications. OSMs have been exploited as imaging agents to transduce biomolecular interactions into second near-infrared fluorescence, chemiluminescence, afterglow or photoacoustic signals, enabling deep-tissue ultrasensitive imaging of biological tissues, disease biomarkers and physiological indexes. By fine-tuning the molecular structures, OSMs can also convert light energy into cytotoxic free radicals or heat, allowing for effective cancer phototherapy. Due to their instant light response and efficient light-harvesting properties, precise regulation of biological activities using OSMs as remote transducers has been demonstrated for protein ion channels, gene transcription and protein activation. In addition to highlighting OSMs as a multifunctional platform for a wide range of biomedical applications, current challenges and perspectives of OSMs in biophotonics are discussed.

Development of organic semiconducting materials for deep-tissue optical imaging, phototherapy and photoactivation

Aggregation-induced emission (AIE) describes a photophysical phenomenon in which molecular aggregates exhibit stronger emission than the single molecules. Over the course of the last 20 years, AIE research has made great strides in material development, mechanistic study and high-tech applications. The achievements of AIE research demonstrate that molecular aggregates show many properties and functions that are absent in molecular species. In this review, we summarize the advances in the field of AIE and its related areas. We specifically focus on the new properties of materials attained by molecular aggregates beyond the microscopic molecular level. We hope this review will inspire more research into molecular ensembles at and beyond the meso level and lead to the significant progress in material and biological science.

Aggregation-Induced Emission: New Vistas at the Aggregate Level

Abnormal enzymatic activities are directly related to the development of cancers. Identifying the location and expression levels of these enzymes in live cancer cells have considerable importance in early-stage cancer diagnoses and monitoring the efficacy of therapies. Small-molecule fluorescent probes have become a powerful tool for the detection and imaging of enzymatic activities in biological systems by virtue of their higher sensitivity, nondestructive fast analysis, and real-time detection abilities. Moreover, due to their structural tailorability, numerous small-molecule enzymatic fluorescent probes have been developed to meet various demands involving real-time tracking and visualizing different enzymes in live cancer cells or in vivo. In this review, we provide an overview of recent advances in small-molecule enzymatic fluorescent probes mainly during the past decade, including the design strategies and applications for various enzymes in live cancer cells. We also highlight the challenges and opportunities in this rapidly developing field of small-molecule fluorescent probes for interventional surgical imaging, as well as cancer diagnosis and therapy.

Recent progresses in small-molecule enzymatic fluorescent probes for cancer imaging

Photodynamic therapy (PDT), which relies on photosensitizers (PS) and light to generate reactive oxygen species to kill cancer cells or bacteria, has attracted much attention in recent years. PSs with both bright emission and efficient singlet oxygen generation have also been used for image-guided PDT. However, simultaneously achieving effective 1 O2 generation, long wavelength absorption, and stable near-infrared (NIR) emission with low dark toxicity in a single PS remains challenging. In addition, it is well known that when traditional PSs are made into nanoparticles, they encounter quenched fluorescence and reduced 1 O2 production. In this contribution, these challenging issues have been successfully addressed through designing the first photostable photosensitizer with aggregation-induced NIR emission and very effective 1 O2 generation in aggregate state. The yielded nanoparticles show very effective 1 O2 generation, bright NIR fluorescence centered at 820 nm, excellent photostability, good biocompatibility, and negligible dark in vivo toxicity. Both in vitro and in vivo experiments prove that the nanoparticles are excellent candidates for image-guided photodynamic anticancer therapy.

A Highly Efficient and Photostable Photosensitizer with Near-Infrared Aggregation-Induced Emission for Image-Guided Photodynamic Anticancer Therapy.

Bacterial infection is one of the most serious physiological conditions threatening human health. There is an increasing demand for more effective bacterial diagnosis and treatment through noninvasive theranostic approaches. Herein, a new strategy is reported to achieve in vivo metabolic labeling of bacteria through the use of MIL-100 (Fe) nanoparticles (NPs) as the nanocarrier for precise delivery of 3-azido-d-alanine (d-AzAla). After intravenous injection, MIL-100 (Fe) NPs can accumulate preferentially and degrade rapidly within the high H2 O2 inflammatory environment, releasing d-AzAla in the process. d-AzAla is selectively integrated into the cell walls of bacteria, which is confirmed by fluorescence signals from clickable DBCO-Cy5. Ultrasmall photosensitizer NPs with aggregation-induced emission characteristics are subsequently designed to react with the modified bacteria through in vivo click chemistry. Through photodynamic therapy, the amount of bacteria on the infected tissue can be significantly reduced. Overall, this study demonstrates the advantages of metal-organic-framework-assisted bacteria metabolic labeling strategy for precise bacterial detection and therapy guided by fluorescence imaging.

Metal–Organic-Framework-Assisted In Vivo Bacterial Metabolic Labeling and Precise Antibacterial Therapy

Chemiluminescence-Guided Cancer Therapy Using a Chemiexcited Photosensitizer

Polymerization-Enhanced Photosensitization

An activatable fluorescent nanoprobe with aggregation-induced emission signature is developed. The nanoprobe is nonfluorescent, but can be induced to emit intensely after reaction with peroxynitrite forming an intramolecular hydrogen bond. Excellent performance for selective in vivo imaging of inflammation with elevated peroxynitrite generation and efficient visualization of in vivo treatment efficacy of anti-inflammatory agents is demonstrated.

Duo Mao

Papers

A Highly Efficient and Photostable Photosensitizer with Near-Infrared Aggregation-Induced Emission for Image-Guided Photodynamic Anticancer Therapy.

Metal–Organic-Framework-Assisted In Vivo Bacterial Metabolic Labeling and Precise Antibacterial Therapy

Chemiluminescence-Guided Cancer Therapy Using a Chemiexcited Photosensitizer

Polymerization-Enhanced Photosensitization

Activatable Fluorescent Nanoprobe with Aggregation‐Induced Emission Characteristics for Selective In Vivo Imaging of Elevated Peroxynitrite Generation