Photodynamic therapy is arising as a noninvasive treatment modality for cancer and other diseases. One of the key factors to determine the therapeutic function is the efficiency of photosensitizers (PSs). Opposed to traditional PSs, which show quenched fluorescence and reduced singlet oxygen production in the aggregate state, PSs with aggregation-induced emission (AIE) exhibit enhanced fluorescence and strong photosensitization ability in nanoparticles. Here, the design principles of AIE PSs and their biomedical applications are discussed in detail, starting with a summary of traditional PSs, followed by a comparison between traditional and AIE PSs to highlight the various design strategies and unique features of the latter. Subsequently, the applications of AIE PSs in photodynamic cancer cell ablation, bacteria killing, and image-guided therapy are discussed using charged AIE PSs, AIE PS molecular probes, and AIE PS nanoparticles as examples. These studies have demonstrated the great potential of AIE PSs as effective theranostic agents to treat tumor or bacterial infection. This review hopefully will spur more research interest in AIE PSs for future translational research.

Photosensitizers with Aggregation-Induced Emission: Materials and Biomedical Applications

Chemodynamic therapy (CDT), a novel cancer therapeutic strategy defined as the treatment using Fenton or Fenton-like reaction to produce •OH in the tumor region, was first proposed by Bu, Shi, and co-workers in 2016. Recently, with the rapid development of Fenton and Fenton-like nanomaterials, CDT has attracted tremendous attention because of its unique advantages: 1) It is tumor-selective with low side effects; 2) the CDT process does not depend on external field stimulation; 3) it can modulate the hypoxic and immunosuppressive tumor microenvironment; 4) the treatment cost of CDT is low. In addition to the Fe-involved CDT strategies, the Fenton-like reaction-mediated CDT strategies have also been proposed, which are based on many other metal elements including copper, manganese, cobalt, titanium, vanadium, palladium, silver, molybdenum, ruthenium, tungsten, cerium, and zinc. Moreover, CDT has been combined with other therapies like chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, and immunotherapy for achieving enhanced anticancer effects. Besides, there have also been studies that extend the application of CDT to the antibacterial field. This review introduces the latest advancements in the nanomaterials-involved CDT from 2018 to the present and proposes the current limitations as well as future research directions in the related field.

Chemodynamic Therapy via Fenton and Fenton-Like Nanomaterials: Strategies and Recent Advances.

Au2Pt-PEG-Ce6 nanoformulation with dual nanozyme activities for synergistic chemodynamic therapy / phototherapy.

Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice. 

/pdf/enhancing-the-therapeutic-efficacy-of-nanoparticles-for-16hldfnu.pdf

Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies

The conversion of nontoxic agents into therapeutic species in situ, just within the disease microenvironment, is the ideal strategy because it can substantially enhance the therapeutic efficacy but mitigate the side effect to normal cells/tissues. The emerging nanocatalytic medicine based on the catalytic Fenton reaction can achieve this goal by triggering a disease-specific catalytic reaction to produce therapeutic reaction oxygen species. Traditional iron-based Fenton nanocatalysts are the dominant agents for triggering in situ reactions and radical nanotherapeutics, but they suffer from low reaction rate and narrow pH operation range, significantly hindering their further biomedical applications and clinical translation. Fortunately, the emergence of iron-free nanocatalysts provides alternative but highly efficient nanoplatforms for achieving desirable Fenton reaction-based nanocatalytic radical therapeutics. This comprehensive review discusses the very-recent progress on the elaborate design, rational construction, purpose-oriented multifunctionalization and catalytic property–performance relationship of iron-free Fenton nanocatalysts (e.g., transition metal-based, precious-metal-based, nonmetal-based nanocatalysts and their composites) for versatile radical nanotherapeutics. The focus is particularly on the underlying catalytic chemistry and mechanism for endowing these iron-free nanocatalysts with unique/specific physicochemical properties for anticancer, antibacterial, antibiofilm and synergistic biomedical applications. Finally, we concentrate on the unresolved critical issues, current challenges and future development direction/prospects of these iron-free Fenton nanocatalysts for future clinical translations.

Catalytic chemistry of iron-free Fenton nanocatalysts for versatile radical nanotherapeutics

The invention discloses a preparation method and an application of a glutathione response vanadium oxide nano-particle. Ammonium metavanadate and hyaluronic acid are synthesized by a one-step method to obtain the nano-particle. The preparation method of the nano-particle is simple, raw materials are low in cost and easy to get, and the vanadium oxide nano-particle modified by the hyaluronic acid has the advantages that the nano-particle is good biocompatibility and has good dispersibility in water solution and the like. The nano-particle has good absorbing ability in a near infrared region after being incubated by glutathione, near-infrared light can be converted into heat energy, and the nano-particle can be used for photothermal therapy and has wide application prospects in the field ofphotothermal therapy for cancers.

Preparation method and application of glutathione response vanadium oxide nano-particle

Although phototherapy has been considered as an emerging and promising technology for cancer therapy, its therapeutic specificity and efficacy are severely limited by nonspecific uptake by normal tissues, tumor hypoxia, and so on. Herein, combination-responsive strategy (CRS) is applied to develop one kind of hyaluronic acid-hybridized Ru nanoaggregates (HA-Ru NAs) for enhanced cancer phototherapy via the reasonable integration of receptor-mediated targeting (RMT) and tumor-microenvironment responsiveness (TMR). In this nanosystem, the HA component endows HA-Ru NAs with RMT characteristic to selectively recognize CD44-overexpressing cancer cells, whereas the Ru nanocomponent makes HA-Ru NAs have TMR therapy activity. Specially, the Ru nanocomponent not only has near-infrared-mediated photothermal and photodynamic functions but also can catalyze H2O2 in tumor tissue to produce O2 for the alleviation of tumor hypoxia and toxic •OH for chemodynamic therapy. Benefitting from these, HA-Ru NAs can be considered as a promising kind of CRS nanoplatforms for synergistic photothermal/photodynamic/chemodynamic therapies of cancer, which will not only effectively improve the phototherapeutic specificity and efficacy but also simplify the therapeutic nanosystems. Meanwhile, HA-Ru NAs can serve as a photoacoustic and computed tomography imaging contrast agent to monitor tumors. Such CRS nanoplatforms hold significant potential in improving therapeutic specificity and efficacy for enhanced cancer phototheranostics.

Receptor-Mediated and Tumor-Microenvironment Combination-Responsive Ru Nanoaggregates for Enhanced Cancer Phototheranostics

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Preparation method and application of glutathione response vanadium oxide nano-particle

Receptor-Mediated and Tumor-Microenvironment Combination-Responsive Ru Nanoaggregates for Enhanced Cancer Phototheranostics