Biofilm has resulted in numerous obstinate clinical infections, posing severe threats to public health. It is urgent to develop original antibacterial strategies for eradicating biofilms. Herein, we develop a surface charge switchable supramolecular nanocarrier exhibiting pH-responsive penetration into an acidic biofilm for nitric oxide (NO) synergistic photodynamic eradication of the methicillin-resistant Staphylococcus aureus (MRSA) biofilm with negligible damage to healthy tissues under laser irradiation. Originally, by integrating the glutathione (GSH)-sensitive α-cyclodextrin (α-CD) conjugated nitric oxide (NO) prodrug (α-CD-NO) and chlorin e6 (Ce6) prodrug (α-CD-Ce6) into the pH-sensitive poly(ethylene glycol) (PEG) block polypeptide copolymer (PEG-(KLAKLAK)2-DA) via host-guest interaction, the supramolecular nanocarrier α-CD-Ce6-NO-DA was finely prepared. The supramolecular nanocarrier shows complete surface charge reversal from negative charge at physiological pH (7.4) to positive charge at acidic biofilm pH (5.5), promoting efficient penetration into the biofilm. Once infiltrated into the biofilm, the nanocarrier exhibits rapid NO release triggered by the overexpressed GSH in the biofilm, which not only produces abundant NO for killing bacteria but also reduces the biofilm GSH level to improve photodynamic therapy (PDT) efficiency. On the other hand, NO can react with reactive oxygen species (ROS) to produce reactive nitrogen species (RNS), further improving the PDT efficiency. Due to the effective penetration into the biofilm and depletion of biofilm GSH, the surface charge switchable GSH-sensitive NO nanocarrier can greatly improve the PDT efficiency at a low photosensitizer dose and laser intensity and cause negligible side effect to healthy tissues. Considering the above advantages, the strategy developed in this work may offer great possibilities to fight against biofilm infections.

Surface Charge Switchable Supramolecular Nanocarriers for Nitric Oxide Synergistic Photodynamic Eradication of Biofilms.

Gas-involving cancer theranostics have attracted considerable attention in recent years due to their high therapeutic efficacy and biosafety. We have reviewed the recent significant advances in the development of stimuli-responsive gas releasing molecules (GRMs) and gas nanogenerators for cancer bioimaging, targeted and controlled gas therapy, and gas-sensitized synergistic therapy. We have focused on gases with known anticancer effects, such as oxygen (O2), carbon monoxide (CO), nitric oxide (NO), hydrogen sulfide (H2S), hydrogen (H2), sulfur dioxide (SO2), carbon dioxide (CO2), and heavy gases that act via the gas-generating process. The GRMs and gas nanogenerators for each gas have been described in terms of the stimulation method, followed by their applications in ultrasound and multimodal imaging, and finally their primary and synergistic actions with other cancer therapeutic modalities. The current challenges and future possibilities of gas therapy and imaging vis-a-vis clinical translation have also been discussed.

Gas-Mediated Cancer Bioimaging and Therapy.

Recent advances of multi-dimensional porphyrin-based functional materials in photodynamic therapy

Interactions between Biomolecules and Zwitterionic Moieties: A Review.

Microbial infectious diseases, especially those caused by new and antibiotic-resistant pathogenic microbes, have become a significant threat to global human health. As an antibiotic-free therapy, phototherapy is a promising approach to treat microbial infections due to its spatiotemporal selectivity, non-invasiveness, minimal side effects, and broad antimicrobial spectrum. Although organic photosensitizer-based antimicrobial phototherapy has been extensively studied over the last decade, there has been no specific review article on this topic yet. It is important and timely to summarize recent research progress in this field. This tutorial review highlights the concept and significance of phototherapy and summarizes innovative types of organic photosensitizers with design strategies to deal with microbial infections. In addition, examples of organic antimicrobial photosensitizers, including antibacterial photosensitizers, antiviral photosensitizers, and antifungal photosensitizers are discussed. Finally, current challenges and future directions of organic photosensitizer-based phototherapy for clinical antimicrobial applications are presented. We believe that this tutorial review will provide general guidance for the future development of efficient photosensitizers and encourage preclinical and clinical studies for phototherapy-mediated antimicrobial treatments.

Organic photosensitizers for antimicrobial phototherapy.

As an emerging area, gas therapy has attracted more and more attention in treating many diseases including cancer. The fabrication of stimuli‐responsive delivery systems with on‐demand release behavior is very promising for precision gas therapy, which can obtain optimal therapeutic performance without gas poisoning risks. In this review, the authors introduce the recent progress in the preparation of different kinds of gas carriers for efficient delivery of gaseous molecules (NO, H2S, CO, O2). Particularly, in order to achieve targeted accumulation of gaseous molecules in tumor tissues, gaseous molecules–integrated nanoparticles were constructed. Most importantly, by combination of gas therapy with other therapeutic modalities such as chemotherapy, photodynamic therapy (PDT), and radiotherapy, various multifunctional nanocarriers have been designed for synergistic cancer therapy. Especially, the recent developments of multifunctional gas‐carrying nanocarriers for synergistic cancer therapy are discussed in detail.

Gas Therapy: An Emerging “Green” Strategy for Anticancer Therapeutics

Rationale: Chronic wounds are one of the common complications of diabetes. Due to the physiological conditions of diabetic patients, these wounds are more susceptible to bacterial infections and the formation of bacterial biofilms, leading to the inefficiency of conventional antibiotic treatment. Methods: Here, hollow mesoporous silica nanoparticles (HMSN) were used as the nanocarriers for co-delivery of azithromycin (AZM) and glucose oxidase (GOX), achieving a remarkable synergistic effect in chronic diabetic wounds. GOX possesses the catalytic ability to consume glucose and produce H2O2 in the diabetic wound area. The down-regulation of local glucose could effectively improve the chronic diabetic wound microenvironment. Meanwhile, the generated H2O2 effectively inhibits bacterial growth and eradicates bacterial biofilms with the synergism of antibiotics AZM. Results: In the bacteria-infected diabetic cutaneous wound models, the reduction of glucose, generation of H2O2, and release of AZM could effectively reduce the bacterial infection and promote the wounds healing. Moreover, there is no obvious toxicity behavior after the treatment. Conclusions: Therefore, the designed nanosystem could effectively accelerate the diabetic wound healing process by the amelioration of the hyperglycemia microenvironment and the eradication of bacterial biofilms around the wounds, making them promising candidates for clinical transformation.

Wound microenvironment-responsive glucose consumption and hydrogen peroxide generation synergistic with azithromycin for diabetic wounds healing

The prevention and control of pathogenic bacteria, fungi, and viruses is a herculean task for all the countries since they greatly threaten global public health. Rapid detection and effective elimination of these pathogens is crucial for the treatment of related diseases. It is urgently demanded to develop new diagnostic and therapeutic strategies to combat bacteria, fungi, and viruses-induced infections. The emergence of aggregation-induced emission (AIE) luminogens (AIEgens) is a revolutionary breakthrough for the treatment of many diseases, including pathogenic infections. In this review, the main focus is on the applications of AIEgens for theranostic treatment of pathogenic bacteria, fungi, and viruses. Due to the AIE characteristic, AIEgens are promising fluorescent probes for the detection of bacteria, fungi, and viruses with excellent sensitivity and photostability. Moreover, AIEgen-based theranostic platforms can be fabricated by introducing bactericidal moieties or designing AIE photosensitizers and AIE photothermal agents. The current strategies and ongoing developments of AIEgens for the treatment of pathogenic bacteria, fungi, and viruses will be discussed in detail.

Aggregation-Induced Emission-Based Platforms for the Treatment of Bacteria, Fungi, and Viruses

ROS-responsive Ag-TiO2 hybrid nanorods for enhanced photodynamic therapy of breast cancer and antimicrobial applications

An adamantane-containing zwitterionic copolymer poly(2-(methacryloyloxy)ethyl phosphorylcholine)-co-poly(2-(methacryloyloxy)ethyl adamantane-1-carboxylate) (poly(MPC-co-MAda)) was prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization The hydrophobic photosensitizer chlorin e6 (Ce6) was conjugated to β-cyclodextrin (β-CD) by glutathione (GSH)-sensitive disulfide bonds The Ce6 conjugated supramolecular prodrug nanocarriers were fabricated due to the host–guest interaction between adamantane and β-CD, which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM) The Ce6 conjugated prodrug nanocarriers showed reduction-responsive release of Ce6, which could result in the activation of Ce6 The generation of cytotoxic reactive oxygen species (ROS) was significantly enhanced due to the activation of Ce6 In additiona, the Ce6 conjugated prodrug nanocarriers could effectively inhibit the proliferation of cancer cells upon light irradiation

Zhe Tang

Papers

Gas Therapy: An Emerging “Green” Strategy for Anticancer Therapeutics

Wound microenvironment-responsive glucose consumption and hydrogen peroxide generation synergistic with azithromycin for diabetic wounds healing

Aggregation-Induced Emission-Based Platforms for the Treatment of Bacteria, Fungi, and Viruses

ROS-responsive Ag-TiO2 hybrid nanorods for enhanced photodynamic therapy of breast cancer and antimicrobial applications

Zwitterionic Reduction-Activated Supramolecular Prodrug Nanocarriers for Photodynamic Ablation of Cancer Cells.