Size-Switchable Ru Nanoaggregates for Enhancing Phototherapy: Hyaluronidase-Triggered Disassembly to Alleviate Deep Tumor Hypoxia.

Hypoxia is a critical factor for restricting photodynamic therapy (PDT) of tumor, and it becomes increasingly severe with increasing tissue depth. Thus, the relief of deep tumor hypoxia is extremely important to improve the PDT efficacy. Herein, tumor microenvironment (TME)-responsive size-switchable hyaluronic acid-hybridized Ru nanoaggregates (HA@Ru NAs) were developed via screening reaction temperature to alleviate deep tumor hypoxia for improving the tumor-specific PDT by the artful integration multiple bioactivated chemical reactions in situ and receptor-mediated targeting (RMT). In this nanosystem, Ru NPs not only enabled HA@Ru NAs to have near infrared (NIR)-mediated photothermal/photodynamic functions, but also could catalyze endogenous H2O2 to produce O2 in situ. More importantly, hyaluronidase (HAase) overexpressed in the TME could trigger disassembly of HA@Ru NAs via the hydrolysis of HA, offering the smart size switch capability from 60 to 15 nm for enhancing tumor penetration. Moreover, the RMT characteristics of HA ensured that HA@Ru NAs could specially enter CD44-overexpressed tumor cells, enhancing tumor-specific precision of phototherapy. Taken together these distinguishing characteristics, smart HA@Ru NAs successfully realized the relief of deep tumor hypoxia to improve the tumor-specific PDT.

H2O2-activated in situ polymerization of aniline derivative in hydrogel for real-time monitoring and inhibition of wound bacterial infection.

Wound is highly susceptible to bacterial infection, which can cause chronic wound and serial complications. However, timely treatment is hampered by the lack of real-time monitoring of wound status and effective therapeutic systems. Herein, in situ biosynthesis of functional conjugated polymer in artificial hydrogel was developed via the utilization of biological microenvironment to realize monitoring in real time of wound infection and inhibition of bacteria for the first time. Specially, an easily polymerizable aniline dimer derivative (N-(3-sulfopropyl) p-aminodiphenylamine, SPA) was artfully in situ polymerized into polySPA (PSPA) in calcium alginate hydrogel, which was initiated via the catalysis of hydrogen peroxide (H2O2) overexpressed in infected wound to produce hydroxyl radical (•OH) by preloaded horseradish peroxidase (HRP). Benefitting from outstanding near infrared (NIR) absorption of PSPA, such polymerization can be ingeniously used for real-time monitoring of H2O2 via naked-eye and photoacoustic signal, as well as NIR light-mediated photothermal inhibition of bacteria. Furthermore, combining the persistent chemodynamic activity of •OH, the in vivo experimental data proved that the wound healing rate was 99.03% on the 11th day after treatment. Therefore, the present work opens the way to manipulate in situ biosynthesis of functional conjugated polymer in artificial hydrogels for overcoming the issues on wound theranostics.