Degradable and Piezoelectric Hollow ZnO Heterostructures for Sonodynamic Therapy and Pro-Death Autophagy.

Piezoelectric materials can generate charges and reactive oxygen species (ROS) under external force stimulation for ultrasound-induced sonodynamic therapy (SDT). However, their poor piezoelectricity, fast electron-hole pair recombination rate, and biological toxicity of piezoelectric materials limit the therapeutic effects of piezoelectric SDT. In this study, hollow ZnO (HZnO) nanospheres were synthesized by using a one-step method.

Red-Light Triggered H-Abstraction Photoinitiators for the Efficient Oxygen-Independent Therapy of Hypoxic Tumors.

The clinical application of photodynamic therapy (PDT) is limited by oxygen-dependence and side effects caused by photosensitizer residues. Photoinitiators based on the H-abstraction reaction can address these challenges because they can generate alkyl radical-killing cells independently of oxygen and undergo rapid bleaching following H-abstraction. Nonetheless, the development of photoinitiators for PDT has been impeded by the absence of effective design strategies.

Activating Iterative Revolutions of the Cancer-Immunity Cycle in Hypoxic Tumors with a Smart Nano-Regulator.

The activation of sequential events in the cancer-immunity cycle (CIC) is crucial for achieving effective antitumor immunity. However, formidable challenges, such as innate and adaptive immune resistance, along with the off-target adverse effects of nonselective immunomodulators, persist. In this study, a tumor-selective nano-regulator named PNBJQ has been presented, focusing on targeting two nonredundant immune nodes: inducing immunogenic cancer cell death and abrogating immune resistance to fully activate endogenous tumor immunity.

Gram-negative bacteria recognition and photodynamic elimination by Zn-DPA based sensitizers.

The abuse and overuse of antibiotics let drug-resistant bacteria emerges. Antibacterial photodynamic therapy (APDT) has shown outstanding merits to eliminate the drug-resistant bacteria via cytotoxic reactive oxygen species produced by irradiating photosensitizer. However, most of photosensitizers are not effective for Gram-negative bacteria elimination.

A PROTAC Augmenter for Photo-Driven Pyroptosis in Breast Cancer.

Proteolysis targeting chimera (PROTAC) has recently emerged as a promising strategy for inducing post-translational knockdown of target proteins in disease treatment. The degradation of bromodomain-containing protein 4 (BRD4), an essential nuclear protein for gene transcription, induced by PROTAC is proposed as an epigenetic approach to treat breast cancer. However, the poor membrane permeability and indiscriminate distribution of PROTAC in vivo results in low bioavailability, limiting its development and application.

Aryl-Modified Pentamethyl Cyanine Dyes at the C2' Position: A Tunable Platform for Activatable Photosensitizers.

Pentamethyl cyanine dyes are promising fluorophores for fluorescence sensing and imaging. However, advanced biomedical applications require enhanced control of their excited-state properties. Herein, a synthetic approach for attaching aryl substituents at the C2' position of the thio-pentamethine cyanine (TCy5) dye structure is reported for the first time.

Lipid Droplet Targeting Type I Photosensitizer for Ferroptosis via Lipid Peroxidation Accumulation.

As an iron-dependent lipid peroxidation (LPO) mediated cell death pathway, ferroptosis offers promises for anti-tumor treatment. Photodynamic therapy (PDT) is an ideal way to generate reactive oxygen species (ROS) for LPO. However, the conventional PDT normally functions on subcellular organelles, such as endoplasmic reticulum, mitochondria, and lysosome, causing rapid cell death before triggering ferroptosis.

Dipicolylamine-Zn Induced Targeting and Photo-Eliminating of Pseudomonas aeruginosa and Drug-Resistance Gram-Positive Bacteria.

The emergence of drug-resistant bacteria, particularly resistant strains of Gram-negative bacteria, such as Pseudomonas aeruginosa, poses a significant threat to public health. Although antibacterial photodynamic therapy (APDT) is a promising strategy for combating drug-resistant bacteria, actively targeted photosensitizers (PSs) remain unknown. In this study, a PS based on dipicolylamine (DPA), known as WZK-DPA-Zn, is designed for the selective identification of P.

Synchronized activating therapeutic nano-agent: Enhancement and tracing for hypoxia-induced chemotherapy.

Prodrug is a potential regime to overcome serious adverse events and off-target effects of chemotherapy agents. Among various prodrug activators, hypoxia stands out owing to the generalizability and prominence in tumor micro-environment. However, existing hypoxia activating prodrugs generally face the limitations of stringent structural requirements, the lack of feedback and the singularity of therapeutic modality, which is imputed to the traditional paradigm that recognition groups must be located at the terminus of prodrugs.

Photoinduced Cuproptosis with Tumor-Specific for Metastasis-Inhibited Cancer Therapy.

Cuproptosis is a novel form of regulated cell death which guarantees to increase the efficacy of existing anticancer treatments that employ traditional apoptotic therapeutics. However, reducing the amount of undesirable Cu ions released in normal tissue and maximizing Cu-induced cuproptosis therapeutic effects at tumor sites are the major challenges. In this study, exploiting the chemical properties of copper ionophores and the tumor microenvironment, a novel method is developed for controlling the valence of copper ions that cause photoinduced cuproptosis in tumor cells.

An Activatable Prodrug Nanosystem for Ultrasound-Driven Multimodal Tumor Therapy and Metastasis Inhibition.

Ultrasound, featuring deep tissue penetration and noninvasiveness, offers a new opportunity to activate functional materials in a tumor-selective manner. However, very few direct ultrasound-responsive redox systems are applicable under therapeutic ultrasound (1 MHz). Herein, the investigations on nanoprodrug of DHE@PEG-SS-DSPE are reported, which exhibit glutathione-activated release of dihydroethidium (DHE) in tumor cells.

A GPX4-targeted photosensitizer to reverse hypoxia-induced inhibition of ferroptosis for non-small cell lung cancer therapy.

Ferroptosis therapy is gradually becoming a new strategy for the treatment of non-small cell lung cancer (NSCLC) because of its active iron metabolism. Because the hypoxic microenvironment in NSCLC inhibits ferroptosis heavily, the therapeutic effect of some ferroptosis inducers is severely limited. To address this issue, this work describes a promising photosensitizer ENBS-ML210 and its application against hypoxia of NSCLC treatment based on type I photodynamic therapy and glutathione peroxidase 4 (GPX4)-targeted ferroptosis.

Highly Efficient Photosensitizers with Molecular Vibrational Torsion for Cancer Photodynamic Therapy.

The development of highly effective photosensitizers (PSs) for photodynamic therapy remains a great challenge at present. Most PSs rely on the heavy-atom effect or the spin-orbit charge-transfer intersystem crossing (SOCT-ISC) effect to promote ISC, which brings about additional cytotoxicity, and the latter is susceptible to the interference of solvent environment. Herein, an immanent universal property named photoinduced molecular vibrational torsion (PVT)-enhanced spin-orbit coupling (PVT-SOC) in PSs has been first revealed.

Photo-Induced Electron Transfer-Triggered Structure Deformation Promoting Near-Infrared Photothermal Conversion for Tumor Therapy.

Photothermal therapy (PTT) is a promising approach to cancer treatment. Heptamethine cyanine (Cy7) is an attractive photothermal reagent because of its large molar absorption coefficient, good biocompatibility, and absorption of near-infrared irradiation. However, the photothermal conversion efficiency (PCE) of Cy7 is limited without ingenious excitation-state regulation.

Piezoelectric Metal-Organic Frameworks Based Sonosensitizer for Enhanced Nanozyme Catalytic and Sonodynamic Therapies.

The regulation of electrostatic electric fields through electrical stimulation is an efficient method to increase the catalytic activity of nanozymes and improve the therapeutic effect of nanozyme catalytic therapy. Piezoelectric materials, which are capable of generating a built-in electric field under ultrasound (US), not only improve the activity of nanozymes but also enable piezoelectric sonodynamic therapy (SDT). In this study, a sonosensitizer based on a Hf-based metal-organic framework (UIO-66) and Au nanoparticles (NPs) was produced.

Photothermal "nano-dot" reactivate "immune-hot" for tumor treatment via reprogramming cancer cells metabolism.

Cancer immunotherapy, despite its enormous application prospect, is trapped in the abnormal lactic acid metabolism of tumor cells that usually causes an immunosuppressive tumor microenvironment (ITM). Inducing immunogenic cell death (ICD) not only sensitizes cancer cells to carcer immunity, but also leads to a great increase in tumor-specific antigens. It improves tumor condition from "immune-cold" to "immune-hot".

A near-infrared GPX4 fluorescent probe for non-small cell lung cancer imaging.

Glutathione peroxidase 4 (GPX4) is overexpressed in non-small cell lung cancer (H1299) cells. In this work, a near-infrared fluorescent probe ENBO-ML210 was developed. and imaging results showed that ENBO-ML210 could target and visualize GPX4 in H1299 cells, exhibiting potential for the diagnosis of non-small lung cancer.

Precise gliomas therapy: Hypoxia-activated prodrugs sensitized by nano-photosensitizers.

Hypoxia is one of the prominent features of solid tumors. Hypoxia activated prodrugs (HAPs), selectively killing hypoxic cells, possess the potential to transform hypoxia from a nuisance to an advantage in precision therapy. Exhibiting a more significant hypoxic microenvironment, gliomas, as the most frequent and incurable neurological tumors, provide HAPs a more attractive therapeutic prospect.

Urea-Bond Scission Induced by Therapeutic Ultrasound for Biofunctional Molecule Release.

Ultrasound-triggered remote control of biomolecular functions in cells provides unique advantages for us to interrogate nature. However, strategies to design therapeutic ultrasound-responsive functional molecules remain elusive, and rare ultrasound-cleavable chemical bonds have been developed to date. Herein, therapeutic ultrasound (1 MHz)-induced scission of urea bonds for drug release is demonstrated for the first time.

Photoredox catalysis may be a general mechanism in photodynamic therapy.

Elucidating the underlying photochemical mechanisms of action (MoA) of photodynamic therapy (PDT) may allow its efficacy to be improved and could set the stage for the development of new classes of PDT photosensitizers. Here, we provide evidence that "photoredox catalysis in cells," wherein key electron transport pathways are disrupted, could constitute a general MoA associated with PDT. Taking the cellular electron donor nicotinamide adenine dinucleotide as an example, we have found that well-known photosensitizers, such as Rose Bengal, BODIPY, phenoselenazinium, phthalocyanine, and porphyrin derivatives, are able to catalyze its conversion to NAD.

ER-Targeting Cyanine Dye as an NIR Photoinducer to Efficiently Trigger Photoimmunogenic Cancer Cell Death.

Endoplasmic reticulum (ER) stress, caused by overproduction of reactive oxygen species (ROS), has been shown to be responsible for immunogenic cell death (ICD). Seeking ROS generator targeting ER is an optimal solution to efficiently induce ER stress. Despite clear indications of demand for ER-targeting photosensitizer, the alternative chemical tools remain limited.

Near-Infrared Light Triggered H Generation for Enhanced Photothermal/Photodynamic Therapy against Hypoxic Tumor.

The principle of photochemical transformation has shown significant inspiration on phototherapy of solid tumors. However, both photodynamic therapy (PDT) and photothermal therapy (PTT) can induce stress response of tumor cells, which draw the attention in recent. Herein, an asymmetric and lollipop like nanostructure consisting of gold nanorod/titanium dioxide (l-TiO -GNR) is developed by controlling single head growth of titanium dioxide (TiO ) on gold nanorods (GNR).

Strong π-π Stacking Stabilized Nanophotosensitizers: Improving Tumor Retention for Enhanced Therapy for Large Tumors in Mice.

Conventional photosensitizers (PSs) often show poor tumor retention and are rapidly cleared from the bloodstream, which is one of the key hindrances to guarantee precise and efficient photodynamic therapy (PDT) in vivo. In this work, a photosensitizer assembly nanosystem that sharply enhances tumor retention up to ≈10 days is present. The PSs are synthesized by meso-substituting anthracene onto a BODIPY scaffold (AN-BDP), which then self-assembles into stable nanoparticles (AN-BDP NPs) with amphiphilic block copolymers due to the strong intermolecular π-π interaction of the anthracene.

New Cy5 photosensitizers for cancer phototherapy: a low singlet-triplet gap provides high quantum yield of singlet oxygen.

Highly efficient triplet photosensitizers (PSs) have attracted increasing attention in cancer photodynamic therapy where photo-induced reactive oxygen species (ROSs, such as singlet oxygen) are produced singlet-triplet intersystem crossing (ISC) of the excited photosensitizer to kill cancer cells. However, most PSs exhibit the fatal defect of a generally less-than-1% efficiency of ISC and low yield of ROSs, and this defect strongly impedes their clinical application. In the current work, a new strategy to enhance the ISC and high phototherapy efficiency has been developed, based on the molecular design of a thio-pentamethine cyanine dye (TCy5) as a photosensitizer.