Pyroptosis-Mediated Synergistic Photodynamic and Photothermal Immunotherapy Enabled by a Tumor-Membrane-Targeted Photosensitive Dimer.

Overcoming the resistance to apoptosis and immunosuppression of tumor cells is a significant challenge in augmenting the effect of cancer immunotherapy. Pyroptosis, a lytic programmed cell-death pathway unlike apoptosis, is considered a type of immunogenic cell death (ICD) that can intensify the ICD process in tumor cells, releasing dramatically increased tumor-associated antigens and damage-associated molecular patterns to promote cancer immunotherapy. Herein, a tumor cell membrane-targeted aggregation-induced emission photosensitive dimer is found to be able to achieve highly efficient ICD under the synergistic effect of photodynamic and photothermal therapy. The photosensitive dimer can efficiently produce type-I reactive oxygen species (ROS) by photodynamic therapy in hypoxic tumor tissue, leading to pyroptosis by direct cell membrane damage, which is further reinforced by its photothermal effect. Furthermore, the enhanced ICD effect based on the dimer can completely eliminate the primary tumor on the seventh day of treatment and can also boost systemic antitumor immunity by generating immune memory, which is demonstrated by the superior antitumor therapeutic effects on both solid tumors and metastatic tumors when healing 4T1 tumor mouse models with poor immunogenicity.

Hypoxia-Responsive Photosensitizer Targeting Dual Organelles for Photodynamic Therapy of Tumors.

Developing safe and precise image-guided photodynamic therapy is a challenge. In this study, the hypoxic properties of solid tumors are exploited to construct a hypoxia-responsive photosensitizer, TPA-Azo. Introducing the azo group into the photosensitizer TPA-BN with aggregation-induced emission quenches its fluorescence. When the nonfluorescent TPA-Azo enters hypoxic tumors, it is reduced by the overexpressed azoreductase to generate a fluorescent photosensitizer TPA-BN with an amino group that exhibits fluorescence-activatable image-guided photodynamic therapy with dual-organelle (lipid droplets and lysosomes) targeting. This design strategy provides a basis for the development of fluorescence-activatable photosensitizers.

Synchronous Imaging in Golgi Apparatus and Lysosome Enabled by Amphiphilic Calixarene-Based Artificial Light-Harvesting Systems.

Artificial supramolecular light-harvesting systems have expanded various properties on photoluminescence, enabling promising applications on cell imaging, especially for imaging in organelles. Supramolecular light-harvesting systems have been used for imaging in some organelles such as lysosome, Golgi apparatus, and mitochondrion, but developing a supramolecular light-harvesting platform for imaging two organelles synchronously still remains a great challenge. Here, we report a series of lower-rim dodecyl-modified sulfonato-calix[4]arene-mediated supramolecular light-harvesting platforms for efficient light-harvesting from three naphthalene diphenylvinylpyridiniums containing acceptors, Nile Red, and Nile Blue. All of the constructed supramolecular light-harvesting systems possess high light-harvesting efficiency. Furthermore, when the two acceptors are loaded simultaneously in a single light-harvesting donor system for imaging in human prostate cancer cells, organelle imaging in lysosome and Golgi apparatus can be realized at the same time with distinctive wavelength emission. Nile Red receives the light-harvesting energy from the donors, reaching orange emissions (625 nm) in lysosome while Nile Blue shows a near-infrared light-harvesting emission at 675 nm in Golgi apparatus in the same cells. Thus, the light harvesting system provides a pathway for synchronously efficient cell imaging in two distinct organelles with a single type of photoluminescent supramolecular nanoparticles.

Light-fueled transient supramolecular assemblies in water as fluorescence modulators.

Dissipative self-assembly, which requires a continuous supply of fuel to maintain the assembled states far from equilibrium, is the foundation of biological systems. Among a variety of fuels, light, the original fuel of natural dissipative self-assembly, is fundamentally important but remains a challenge to introduce into artificial dissipative self-assemblies. Here, we report an artificial dissipative self-assembly system that is constructed from light-induced amphiphiles. Such dissipative supramolecular assembly is easily performed using protonated sulfonato-merocyanine and chitosan based molecular and macromolecular components in water. Light irradiation induces the assembly of supramolecular nanoparticles, which spontaneously disassemble in the dark due to thermal back relaxation of the molecular switch. Owing to the presence of light-induced amphiphiles and the thermal dissociation mechanism, the lifetimes of these transient supramolecular nanoparticles are highly sensitive to temperature and light power and range from several minutes to hours. By incorporating various fluorophores into transient supramolecular nanoparticles, the processes of aggregation-induced emission and aggregation-caused quenching, along with periodic variations in fluorescent color over time, have been demonstrated. Transient supramolecular assemblies, which act as fluorescence modulators, can also function in human hepatocellular cancer cells.

An Efficient Near-Infrared Emissive Artificial Supramolecular Light-Harvesting System for Imaging in the Golgi Apparatus.

Light-harvesting systems are an important way for capturing, transferring and utilizing light energy. It remains a key challenge to develop highly efficient artificial light-harvesting systems. Herein, we report a supramolecular co-assembly based on lower-rim dodecyl-modified sulfonatocalix[4]arene (SC4AD) and naphthyl-1,8-diphenyl pyridinium derivative (NPS) as a light-harvesting platform. NPS as a donor shows significant aggregation induced emission enhancement (AIEE) after assembling with SC4AD. Upon introduction of Nile blue (NiB) as an acceptor into the NPS-SC4AD co-assembly, the light-harvesting system becomes near-infrared (NIR) emissive (675 nm). Importantly, the NIR emitting NPS-SC4AD-NiB system exhibits an ultrahigh antenna effect (33.1) at a high donor/acceptor ratio (250:1). By co-staining PC-3 cells with a Golgi staining reagent, NBD C6 -ceramide, NIR imaging in the Golgi apparatus has been demonstrated using these NIR emissive nanoparticles.