High Reactive Oxygen Species Generation Research Articles

Small‐Bandgap Transducers Induced Carrier Separation for In Situ Dual‐Amplified Tumor Oxidative Stress

AbstractThe inherent and unique charge‐carrier release characteristics of piezoelectric sonosensitizers with desired bandgap can be leveraged to initiate reactive oxygen species (ROS) reactions that have considerable potential for sonodynamic therapy (SDT). In this study, a bimetallic Bi4NbO8Br‐polyvinylpyrrolidone (BNOBP) with a small bandgap (2.45 eV) is synthesized as a potential piezoelectric sonosensitizer. The robust interactions within and between the Bi─O and Nb─O layers narrow the bandgap, facilitating carrier transfer. Concurrently, compared with that of TiO2 and BiOBr, BNOBP exhibits a rapid acoustoelectric response and desirable electron–hole separation efficiency, enabling the generation of ·O2− under ultrasound (US) irradiation. Notably, BNOBP alleviates the overexpression of glutathione (GSH) in tumors and prevents the consumption of the generated ROS by GSH. Combining the previous small bandgap endow the high ROS generation efficiency, this study provides a paradigm for in situ regulation of oxidative stress levels in tumor tissue microenvironment based on bimetallic piezoelectric sonosensitizers.

Melanin-Ce6-loaded polydopamine nanoparticles-based enhanced phototherapy for B16 melanoma cancer cells

Melanoma is one of the most aggressive and lethal types of cancer owing to its metastatic propensity and chemoresistance property. An alternative therapeutic option is photodynamic and photothermal therapies (PDT/PTT), which employ near-infrared (NIR) light to generate heat and reactive oxygen species (ROS). As per previous reports, Melanin (Mel), and its synthetic analogs (i.e. polydopamine nanoparticles) can induce NIR light-mediated heat energy, thereby selectively targeting and ameliorating cancer cells. Similarly, chlorin e6 (Ce6) also has high ROS generation ability and antitumor activity against various types of cancer. Based on this tenet, In the current study, we have encapsulated Mel-Ce6 in a polydopamine (PDA) nanocarrier (MCP NPs) synthesized by the oxidation polymerization method. The hydrodynamic diameter of the synthesized spherical MCP NPs was 139 ± 10 nm. The MCP NPs, upon irradiation with NIR 690 nm laser for 6 min, showed photothermal efficacy of more than 50 °C. Moreover, the red fluorescence in the MCP NPs due to Ce6 can be leveraged for diagnostic purposes. Further, the MCP NPs exhibited considerable biocompatibility with the L929 cell line and exerted nearly 70% ROS-mediated cytotoxicity on the B16 melanoma cell line after the laser irradiation. Thus, the prepared MCP NPs could be a promising theranostic agent for treating the B16 melanoma cancer.

Less is More: Asymmetric D-A Type Agent to Achieve Dynamic Self-Assembled Nanoaggregates for Long-Acting Photodynamic Therapy.

To enhance the phototheranostic performance, agents with high reactive oxygen species (ROS) generation, good tumor-targeting ability, and prolonged retention are urgently needed. However, symmetric donor-acceptor (D-A) type agents usually produce spherical nanoaggregates, leading to good tumor targeting but inferior retention. Rod-like nanoaggregates are desired to extend their retention in tumors; however, this remains a challenge. In particular, agents with dynamically changeable shapes that integrate merits of different morphologies are seldomly reported. Therefore, self-assembled organic nanoaggregates with smart shape tunability are designed here using an asymmetric D-A type TIBT. The photoluminescence quantum yield in solids is up to 52.24% for TIBT. TIBT also exhibits high ROS generation in corresponding nanoaggregates (TIBT-NCs). Moreover, dynamic self-assembly in shape changing from nanospheres to nanorods occurrs in TIBT-NCs, contributing to the enhancement of ROS quantum yield from 0.55 to 0.72. In addition, dynamic self-assembly can be observed for both in vitro and in vivo, conferring TIBT-NCs with strong tumor targeting and prolonged retention. Finally, efficient photodynamic therapy to inhibit tumor growth is achieved in TIBT-NCs, with an inhibition rate of 90%. This work demonstrates that asymmetric D-A type agents can play significant roles in forming self-assembled organic nanoaggregates, thus showing great potential in long-acting cancer therapy.

Near‐Infrared Active Tri‐nanohybrid for Enhanced Energy Harvesting

AbstractEfficient energy harvesting through full solar spectrum utilization has been considered a promising solution to world energy and environmental issues. In this direction, lead sulphide (PbS) quantum dot (QD) based hybrid materials find greater application due to their near‐infrared (NIR) active photo response. Slower charge injection and inefficient charge separation limit photoactive response of such NIR active low band gap semiconductor like PbS QDs. Moreover, constructing dual charge transfer pathways in a PbS QDs based nanocomposite through the formation of hybrids with suitable materials can be advantageous in suppressing the charge recombination. In this work, we have synthesized a nanocomposite after decorating the PbS‐QDs with semiconducting TiO2 nanoparticles modified with multiwall carbon nanotubes (MWCNT) and thus forming the tri‐hybrid (PbS‐TiO2‐MWCNT) nanocomposites. The enhanced photo‐activities of the tri‐hybrid, as compared to di‐hybrids like PbS‐TiO2, PbS‐MWCNT were confirmed by the steady state, time‐resolved photoluminescence (TRPL) measurements and reactive oxygen species (ROS) generation measurements. Higher ROS generation in the tri‐hybrid has been correlated with a faster interfacial electron transfer due to the dual charge injection pathway of PbS QD to TiO2 and MWCNT. The enhanced activity of the trio‐hybrid has also been analyzed from the first principal calculations in light of an efficient interfacial electron transfer as a result of the dual charge injection pathway. The photoelectrochemical water‐spilling response of the photoanodes in terms of photocurrent density, electrochemical impedance, and Mott–Schottky measurements on PbS‐TiO2 and PbS‐TiO2‐MWCNT photoanodes reveal that a combination of MWCNT and TiO2 exhibits an increase in electrical double layer capacitance, decrease in series resistance and enhancement of carrier density with NIR illumination at the heterojunction. Overall, all the dynamical studies at the interface of the trihybrid‐based photoanodes demonstrate its potential of utilization as a futuristic NIR‐ active photoelectrochemical water‐splitting material.

Novel near-infrared BODIPY-cyclodextrin complexes for photodynamic therapy

To meet the requirements of diagnosis and treatment, photodynamic therapy (PDT) is a promising cancer treatment with less side-effect. A series of novel BODIPY complexes (BODIPY-CDs) served as PDT agents were first reported to enhance the biocompatibility and water solubility of BODIPY matrix through the click reaction of alkynyl-containing BODIPY and azide-modified cyclodextrin (CD). BODIPY-CDs possessed superior water solubility due to the introduction of CD and their fluorescence emission apparently redshifted (>90 nm) on account of triazole units as the linkers compared to alkynyl-containing BODIPY. Moreover, all the BODIPY-CDs were no cytotoxicity toward NIH 3T3 in different drug concentrations from 12.5 to 200 μg/mL, and had a certain inhibitory effect on tumor HeLa cells. Particularly, BODIPY-β-CD exhibited high reactive oxygen species generation and excellent photodynamic therapy activity against HeLa cells compared to other complexes. The cell viability of BODIPY-β-CD was dramatically reduced up to 20% in the concentration of 100 μg/mL upon 808 nm laser irradiation. This architecture might provide a new opportunity to develop valuable photodynamic therapy agents for tumor cells.

Precise molecular engineering for the preparation of pyridinium photosensitizers with efficient ROS generation and photothermal conversion.

Organic photosensitizers (PSs) with aggregation-induced emission properties have great development potential in the integrated application of multi-mode diagnosis and treatment of photodynamic therapy (PDT) and photothermal therapy (PTT). However, preparing high-quality PSs with both optical and biological properties, high reactive oxygen species (ROS) and photothermal conversion ability are undoubtedly a great challenge. In this work, a series of pyridinium AIE PSs modified with benzophenone have been synthesized. A wide wavelength range of fluorescent materials was obtained by changing the conjugation and donor-acceptor strength. TPAPs5 has a significant advantage over similar compounds, and we have also identified the causes of high ROS generation and high photothermal conversion in terms of natural transition orbitals, excited state energy levels, ground-excited state configuration differences and recombination energy. Interestingly, migration of target sites was also found in biological imaging experiments, which also provided ideas for the design of double-targeted fluorescent probes. Therefore, the present work proposed an effective molecular design strategy for synergistic PDT and PTT therapy.

Environmental Chemical-Induced Reactive Oxygen Species Generation and Immunotoxicity: A Comprehensive Review.

Significance: Reactive oxygen species (ROS), the reactive oxygen-carrying chemicals moieties, act as pleiotropic signal transducers to maintain various biological processes/functions, including immune response. Increased ROS production leads to oxidative stress, which is implicated in xenobiotic-induced adverse effects. Understanding the immunoregulatory mechanisms and immunotoxicity is of interest to developing therapeutics against xenobiotic insults. Recent Advances: While developmental studies have established the essential roles of ROS in the establishment and proper functioning of the immune system, toxicological studies have demonstrated high ROS generation as one of the potential mechanisms of immunotoxicity induced by environmental chemicals, including heavy metals, pesticides, aromatic hydrocarbons (benzene and derivatives), plastics, and nanoparticles. Mitochondrial electron transport and various signaling components, including NADH oxidase, toll-like receptors (TLRs), NF-κB, JNK, NRF2, p53, and STAT3, are involved in xenobiotic-induced ROS generation and immunotoxicity. Critical Issues: With many studies demonstrating the role of ROS and oxidative stress in xenobiotic-induced immunotoxicity, rigorous and orthogonal approaches are needed to achieve in-depth and precise understanding. The association of xenobiotic-induced immunotoxicity with disease susceptibility and progression needs more data acquisition. Furthermore, the general methodology needs to be possibly replaced with high-throughput precise techniques. Future Directions: The progression of xenobiotic-induced immunotoxicity into disease manifestation is not well documented. Immunotoxicological studies about the combination of xenobiotics, age-related sensitivity, and their involvement in human disease incidence and pathogenesis are warranted. Antioxid. Redox Signal. 40, 691-714.

Engineering Diselenide-IR780 Homodimeric Nanoassemblies with Enhanced Photodynamic and Immunotherapeutic Effects for Triple-Negative Breast Cancer Treatment.

Photodynamic therapy (PDT) has emerged as an efficient approach for non-invasive cancer treatment. However, organic small-molecule photosensitizers are often associated with defects in hydrophobicity, poor photostability, and aggregation-caused quenching, which limit their application. Usually, the carrier-assisted drug delivery system is a common strategy to solve the above obstacles, but additional carrier material could increase the risk of potential biological toxicity. The carrier-free drug delivery system with easy preparation and high drug-loading capability is proposed subsequently as a potential strategy to develop the clinical use of hydrophobic drugs. Herein, we rationally designed three IR780-based carrier-free nanosystems formed by carbon/disulfide/diselenide bond conjugated IR780-based homodimers. The IR780-based homodimers could self-assemble to form nanoparticles (DC-NP, DS-NP, DSe-NP) and exhibited higher reactive oxygen species generation capability and photostability than free IR780, in which DSe-NP with 808 nm laser irradiation performed best and resulted in the strongest cytotoxicity to 4T1 cells. Meanwhile, the glutathione consumption ability of DSe-NP boosted its PDT effect and then induced excessive oxidative stress of 4T1 cells, increasing antitumor efficacy by enhancing immunogenic cell death further. In tumor-bearing mice, DSe-NP displayed obvious tumor site accumulation, which obviously inhibited tumor growth and metastasis, and enhanced the immunological effect by effectively inducing dendritic cells to mature and activating T lymphocytes and natural killer cells. In summary, our study presented an IR780-based carrier-free nanodelivery system for a combination of PDT and immunity therapy and established expanding the application of organic small-molecule photosensitizers by an approach of carrier-free drug delivery system.

Meticulously Designed Carbon Dots as Photo-Triggered RNA-Destroyer for Evoking Pyroptosis.

An ideal photosensitizer for photodynamic therapy should not only possess high reactive oxygen species (ROS) generation efficiency but also maximize utilization of the in situ produced ROS species, where the latter is closely related to its intracellular location. However, rational design of such photosensitizer without tedious conjugation procedures remains a grand challenge. Here, we report the one-pot preparation of carbon dots (CDs)-based photosensitizer from levofloxacin and neutral red featuring both high 1O2 quantum yield (φΔ = 38.85%) and superior RNA selectivity. Moreover, the φΔ value shows a further 40% improvement and reaches 54.33% in response to RNA binding. Owing to these combined attributes, the CDs could exert great damage to the cellular RNA system (termed the RNA-destroyer) under extremely low dosage of light irradiation (15 mW cm-2, 1 min). It induces pyroptotic cell death and causes rapid release of different cytokines that served as molecular markers in photodynamic immunotherapy. This work represents the meticulously designed CDs with high ROS generation and utilization efficiency via good organization of the photosensitive and targeting modularity. Moreover, it is the first CDs-based pyroptosis inducer to the best of our knowledge.

A tumor-microenvironment-activated nanoplatform of modified SnFe2O4 nanozyme in scaffold for enhanced PTT/PDT tumor therapy

Phototherapy has attracted widespread attention for cancer treatment due to its noninvasiveness and high selectivity. However, severe hypoxia, overexpressed glutathione and high levels of hydrogen peroxide (H2O2) of tumor microenvironment limit the antitumor efficiency of phototherapy. Herein, inspired by the specific response of nanozymes to the tumor microenvironment, a simple and versatile nanozyme-mediated synergistic dual phototherapy nanoplatform is constructed. In this study, tin ferrite (SnFe2O4, SFO) nanozyme as a photosensitizer was surface modified with polydopamine (denoted as P-SFO) and incorporated into poly(l-lactide) to fabricate an antitumor scaffold fabricated by selective laser sintering. On one hand, SFO nanozyme could act as a photoabsorber to convert light energy into heat for photothermal therapy (PTT). On the other hand, it played a role of photosensitizer in transferring the photon energy to generate reactive oxygen species (ROS) for photodynamic therapy (PDT). Importantly, its multivalent metal ions redox couples would decompose H2O2 into O2 for enhancing O2-dependent PDT and consume glutathione to relieve antioxidant capability of the tumors. Besides, polydopamine as a photothermal conversion agent further enhanced the photothermal performance of SFO. The results revealed the PLLA/P-SFO scaffold possessed a photothermal conversion efficiency of 43.52% for PTT and a high ROS generation capacity of highly toxic ·O2− and ·OH for PDT. Consequently, the scaffold displayed a prominent phototherapeutic effect with antitumor rate of 96.3%. In addition, the PLLA/P-SFO scaffolds possessed good biocompatibility for cell growth. These advantages endow PLLA/P-SFO scaffold with extensive applications in biomedical fields and opened up new avenue towards nanozyme-mediated synergistic phototherapy.

Constructing efficient and photostable photosensitizer with aggregation-induced emission by introducing highly electronegative nitrogen atom for photodynamic therapy

Photodynamic therapy (PDT) has drawn considerable attention owning to many unique advantages, such as precise controllability, noninvasiveness, high efficiency and spatiotemporal selectivity. However, most of the currently utilized photosensitizers (PSs) have drawbacks of weak light absorption for excitation and low reactive oxygen species (ROS) generation ability. In this contribution, through introducing highly electronegative nitrogen atom, two photostable photosensitizers are designed to display high absorption coefficient and efficient ROS generation ability. The yield BTPTT-CNTPE nanoparticles show good performance of excellent photostability, high ROS generation efficiency, negligible dark toxicity and high absorption coefficient. Subsequent PDT experiments both in vitro and in vivo prove that BTPTT-CNTPE nanoparticles are promising candidates for PDT anticancer therapy.

Catalytic Ozonation of Polluter Benzene from -20 to >50 °C with High Conversion Efficiency and Selectivity on Mullite YMn2O5.

Catalytic decomposition of aromatic polluters at room temperature represents a green route for air purification but is currently challenged by the difficulty of generating reactive oxygen species (ROS) on catalysts. Herein, we develop a mullite catalyst YMn2O5 (YMO) with dual active sites of Mn3+ and Mn4+ and use ozone to produce a highly reactive O* upon YMO. Such a strong oxidant species on YMO shows complete removal of benzene from -20 to >50 °C with a high COx selectivity (>90%) through the generated reactive species O* on the catalyst surface (60 000 mL g-1 h-1). Although the accumulation of water and intermediates gradually lowers the reaction rate after 8 h at 25 °C, a simple treatment by ozone purging or drying in the ambient environment regenerates the catalyst. Importantly, when the temperature increases to 50 °C, the catalytic performance remains 100% conversion without any degradation for 30 h. Experiments and theoretical calculations show that such a superior performance stems from the unique coordination environment, which ensures high generation of ROS and adsorption of aromatics. Mullite's catalytic ozonation degradation of total volatile organic compounds (TVOC) is applied in a home-developed air cleaner, resulting in high efficiency of benzene removal. This work provides insights into the design of catalysts to decompose highly stable organic polluters.

PH-sensitive charge-conversion cinnamaldehyde polymeric prodrug micelles for effective targeted chemotherapy of osteosarcoma in vitro.

Introduction: Chemotherapy is a common strategy for the treatment of osteosarcoma. However, its therapeutic efficacy is not ideal due to the low targeting, lowbioavailability, and high toxicity of chemotherapy drugs. Nanoparticles can improve the residence time of drugs at tumor sites through targeted delivery. This new technology can reduce the risk to patients and improve survival rates. To achieve this goal, we developed a pHsensitive charge-conversion polymeric micelle [mPEG-b-P(C7-co-CA) micelles] for osteosarcoma-targeted delivery of cinnamaldehyde (CA). Methods: First, an amphiphilic cinnamaldehyde polymeric prodrug [mPEG-b-P(C7-co-CA)] was synthesized through Reversible Addition-Fragmentation Chain Transfer Polymerization (RAFT) polymerization and post-modification, and self-assembled into mPEG-b-P(C7-co-CA) micelles in an aqueous solution. The physical properties of mPEG-b-P(C7-co-CA) micelles, such as critical micelle concentration (CMC), size, appearance, and Zeta potential were characterized. The CA release curve of mPEG-b-P(C7-co-CA) micelles at pH 7.4, 6.5 and 4.0 was studied by dialysis method, then the targeting ability of mPEG-b-P(C7-co-CA) micelles to osteosarcoma 143B cells in acidic environment (pH 6.5) was explored by cellular uptakeassay. The antitumor effect of mPEG-b-P(C7-co-CA) micelles on 143B cells in vitro was studied by MTT method, and the level of reactive oxygen species (ROS) in 143B cells after mPEG-b-P(C7-co-CA) micelles treatment was detected. Finally, the effects of mPEG-b-P(C7-co-CA) micelles on the apoptosis of 143B cells were detected by flow cytometry and TUNEL assay. Results: An amphiphilic cinnamaldehyde polymeric prodrug [mPEG-b-P(C7-co-CA)] was successfully synthesized and self-assembled into spheric micelles with a diameter of 227 nm. The CMC value of mPEG-b-P(C7-co-CA) micelles was 25.2 mg/L, and it showed a pH dependent release behavior of CA. mPEG-b-P(C7-co-CA) micelles can achieve chargeconversion from a neutral to a positive charge with decreasing pHs. This charge-conversion property allows mPEG-b-P(C7-co-CA) micelles to achieve 143B cell targeting at pH 6.5. In addition, mPEG-b-P(C7-co-CA) micelles present high antitumor efficacy and intracellular ROS generation at pH 6.5 which can induce 143B cell apoptosis. Discussion: mPEG-b-P(C7-co-CA) micelles can achieve osteosarcoma targeting effectively and enhance the anti-osteosarcoma effect of cinnamaldehyde in vitro. This research provides a promising drug delivery system for clinical application and tumor treatment.

Wavelength engineerable porous organic polymer photosensitizers with protonation triggered ROS generation

Engineering excitation wavelength of photosensitizers (PSs) for enhanced reactive oxygen species (ROS) generation has inspired new windows for opportunities, enabling investigation of previously impracticable biomedical and photocatalytic applications. However, controlling the wavelength corresponding to operating conditions remains challenging while maintaining high ROS generation. To address this challenge, we implement a wavelength-engineerable imidazolium-based porous organic photocatalytic ROS generation system (KUP system) via a cost-effective one-pot reaction. Remarkably, the optimal wavelength for maximum performance can be tuned by modifying the linker, generating ROS despite the absence of metal ions and covalently attached heavy atoms. We demonstrate that protonated polymerization exclusively enables photosensitization and closely interacts with oxygen related to the efficiency of photosensitizing. Furthermore, superior tumor eradication and biocompatibility of the KUP system were confirmed through bioassays. Overall, the results document an unprecedented polymerization method capable of engineering wavelength, providing a potential basis for designing nanoscale photosensitizers in various ROS-utilizing applications.

Recent Advances of Photoactive Near-Infrared Carbon Dots in Cancer Photodynamic Therapy

Photodynamic therapy (PDT) is a treatment that employs exogenously produced reactive oxygen species (ROS) to kill cancer cells. ROS are generated from the interaction of excited-state photosensitizers (PSs) or photosensitizing agents with molecular oxygen. Novel PSs with high ROS generation efficiency is essential and highly required for cancer photodynamic therapy. Carbon dots (CDs), the rising star of carbon-based nanomaterial family, have shown great potential in cancer PDT benefiting from their excellent photoactivity, luminescence properties, low price, and biocompatibility. In recent years, photoactive near-infrared CDs (PNCDs) have attracted increasing interest in this field due to their deep therapeutic tissue penetration, superior imaging performance, excellent photoactivity, and photostability. In this review, we review recent progress in the designs, fabrication, and applications of PNCDs in cancer PDT. We also provide insights of future directions in accelerating the clinical progress of PNCDs.

Synthesis and biological evaluation of salophen nickel(II) and cobalt(III) complexes as potential anticancer compounds.

Recent in vitro investigations of N,N'-bis(salicylidene)-1,2-phenylenediamine (SAP) iron(III) complexes substituted with alkyl (ethyl, propyl, butyl) carboxylates at position 4 in tumor and leukemia cells revealed strong cytotoxic activity. In continuation of this study, analogous nickel(II) and cobalt(III) complexes were synthesized and tested in HL-60 leukemia, and cisplatin-sensitive and -resistant A2780 ovarian cancer cell lines. The biological activity depended on the extent of cellular uptake and the formation of reactive oxygen species (ROS). Inactive [(Ni(II)SAP] complexes (1-3) only marginally accumulated in tumor cells and did not induce ROS. The cellular uptake of [Co(III)SAP]Cl complexes (4-6) into the cells depended on the length of the ester alkyl chain (ethyl, 4 < propyl, 5 < butyl, 6). The cytotoxicity correlated with the presence of ROS. The low cytotoxic complex 4 induced only few ROS, while 5 and 6 caused a good to outstanding antiproliferative activity, exerted high ROS generation, and induced cell death after 48 h. Necrostatin-1 prevented the biological effects, proving necroptosis as part of the mode of action. Interestingly, the effects of 5 and 6 were not reversed by Ferrostatin-1, but even enhanced upon simultaneous application to the tumor cells.

Novel aggregation-induced emission-photosensitizers with built-in capability of mitochondria targeting and glutathione depletion for efficient photodynamic therapy.

Owing to its non-invasive feature and excellent therapeutic effect, photodynamic therapy has received considerable interest in cancer therapy. However, the therapeutic efficacy of photodynamic therapy is limited by some intrinsic drawbacks of photosensitizers such as aggregation-caused quenching and non-specificity towards cellular organelles. Moreover, the overexpressed glutathione in tumour cells which exhibits a potent scavenging effect on reactive oxygen species generated during the photodynamic therapy process also reduces the efficacy of photodynamic therapy. Therefore, the synthesis of aggregation-induced emission based photosensitizers with cellular organelle targeting and glutathione-depletion capability is highly desirable in photodynamic therapy. Here, two new aggregation-induced emission based photosensitizers namely tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid (TPEPy-BA) and tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid pinacol ester (TPEPy-BE) were synthesized which easily aggregated under aqueous conditions and showed bright emission in the near infra-red region. Furthermore, these photosensitizers were encapsulated into an amphiphilic block copolymer (DSPE-PEG) to improve the aqueous stability and cellular internalization of photosensitizers. The developed photosensitizer nanoparticles showed high reactive oxygen species generation efficacy, mitochondria-targeting and glutathione-depletion capability. The results showed that tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid pinacol ester nanoparticles exhibited a highly efficient photodynamic ablation of MCF-7 cells compared to tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid nanoparticles, upon white light irradiation, due to its high intracellular reactive oxygen species generation efficiency and mitochondria-dysfunction ability. Moreover, tetraphenylethylene-1-phenyvinyl-pyridine-phenylboronic acid pinacol ester nanoparticles produced a glutathione-depleting adjuvant, quinone methide, which greatly reduced the glutathione level in cancer cells, thus enhancing the efficacy of photodynamic therapy. This study provides a new strategy for the synthesis of aggregation-induced emission based photosensitizers with combined mitochondria-targeting and glutathione-depletion capability for efficacious photodynamic therapy.

Stanene nanosheets-based hydrogel for sonodynamic treatment of drug-resistant bacterial infection

Antibacterial resistance has caused a serious global threat to human health. It is essential to exploit a highly effective method for the treatment of drug-resistant bacterial infections. Herein, a sonodynamic antibacterial strategy based on stanene nanosheets (SnNSs) is developed. The obtained SnNSs have a classic nanosheet structure and exhibit excellent a high reactive oxygen species generation ability under ultrasound. Then, SnSNs are assembled with a thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PLEL) to obtain Sn@hydrogel. Sn@hydrogel presents good sonodynamic antibacterial activity, thus improving the wound healing effect. The in vivo evaluation of full-layer methicillin-resistant staphylococcus aureus (MRSA) infected wound model shows that Sn@hydrogel has high anti-infection and wound healing effects. This stanene nanosheets-based hydrogel has good sonodynamic antibacterial effect, which provides a new way to effectively reduce bacterial infection and promote wound healing.

Modulation of reactive oxygen species to enhance sonodynamic therapy

Reactive oxygen species (ROS), involving in many biological reactions, play an important role in disease treatment. Among the various ROS-based therapeutic modalities, sonodynamic therapy (SDT) stands out with its unique advantages. In turn, the SDT efficacy is mainly dependent on the ROS levels in the disease microenvironment. Therefore, in recent years, researchers have extensively investigated SDT with high ROS generation capacity. In this review, we focus on effective strategies to improve the therapeutic efficiency of SDT by modulating ROS, overview the basic mechanisms of ROS generation by sonosensitizers, highlight the rational design of sonosensitizers, and summarize strategies to improve the SDT efficacy by modulating disease microenvironment. In addition, multiple ROS synergistic treatment modalities and the prospect of SDT are discussed. We believe that the understanding and exploration of SDT enhancement strategies will facilitate the clinical translation of SDT.

An AIE probe for long-term plasma membrane imaging and membrane-targeted photodynamic therapy

Two red-emissive luminogens (TPTH and TPTB) with typical aggregation-induced emission characteristics were developed. By introducing the heavy atom of Br at the end of alkyl chain, TPTB exhibited higher reactive oxygen species generation efficiency through both types I and II pathways. Due to its excellent biocompatibility and proper lipophilicity, TPTB could be used for long-term cell membrane staining and this staining ability was independent of the change of plasma membrane potential. Furthermore, TPTB could ablate the cancer cells through cell membrane-targeted photodynamic therapy.