Ultrasound-Switchable Nanozyme Augments Sonodynamic Therapy against Multidrug-Resistant Bacterial Infection.

Ultrasound (US)-driven sonodynamic therapy (SDT) has demonstrated wide application prospects in the eradication of deep-seated bacterial infections due to its noninvasiveness, site-confined irradiation, and high-tissue-penetrating capability. However, the ineffective accumulation of sonosensitizers at the infection site, the hypoxic microenvironment, as well as rapid depletion of oxygen during SDT greatly hamper the therapeutic efficacy of SDT. Herein, an US-switchable nanozyme system was proposed for the controllable generation of catalytic oxygen and sonosensitizer-mediated reactive oxygen species during ultrasound activation, thereby alleviating the hypoxia-associated barrier and augmenting SDT efficacy. This nanoplatform (Pd@Pt-T790) was easily prepared by bridging enzyme-catalytic Pd@Pt nanoplates with the organic sonosensitizer meso-tetra(4-carboxyphenyl)porphine (T790). It was really interesting to find that the modification of T790 onto Pd@Pt could significantly block the catalase-like activity of Pd@Pt, whereas upon US irradiation, the nanozyme activity was effectively recovered to catalyze the decomposition of endogenous H2O2 into O2. Such "blocking and activating" enzyme activity was particularly important for decreasing the potential toxicity and side effects of nanozymes on normal tissues and has potential to realize active, controllable, and disease-loci-specific nanozyme catalytic behavior. Taking advantage of this US-switchable enzyme activity, outstanding accumulation in infection sites, as well as excellent biocompatibility, the Pd@Pt-T790-based SDT nanosystem was successfully applied to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced myositis, and the sonodynamic therapeutic progression was noninvasively monitored by photoacoustic imaging and magnetic resonance imaging. The developed US-switchable nanoenzyme system provides a promising strategy for augmenting sonodynamic eradication of deep-seated bacterial infection actively, controllably, and precisely.

A trustworthy CpG nanoplatform for highly safe and efficient cancer photothermal combined immunotherapy.

Palladium nanosheets (Pd NSs) have recently attracted increasing research interest in the biomedical field due to their excellent near-infrared absorption, photothermal conversion capability and biocompatibility. However, the application of Pd NSs in immunotherapy has not been reported. Here, Pd NSs were used as the carriers of immunoadjuvant CpG ODNs for not only efficient delivery of CpG but also for enhancing the immunotherapeutic effects of CpG by the Pd NS-based photothermal therapy (PTT). Pd NSs had no influence on the immune system, and the prepared Pd-CpG nanocomposites, especially Pd(5)-CpG(PS), could significantly increase the uptake of CpG by immune cells and enhance the immunostimulatory activity of CpG in vitro and in vivo. With the combination of Pd(5)-CpG(PS) mediated PTT and immunotherapy, highly efficient tumor inhibition was achieved and the survival rate of the tumor-bearing mice was greatly increased depending on Pd(5)-CpG(PS) with safe near-infrared (NIR) irradiation (808 nm laser, 0.15 W cm-2). Importantly, the combination therapy induced tumor cell death and released tumor-associated antigens, which could be effectively taken up and presented by antigen presenting cells with the assistance of CpG, leading to increased TNF-α and IL-6 production and enhanced cytotoxic T lymphocyte (CTL) activity. This work provides a new paradigm of utilizing photothermal nanomaterials for safe and highly efficient cancer photothermal combined immunotherapy.