The production of reactive oxygen species, persistent inflammation, bacterial infection, and recurrence after a tumor resection has become the main challenge in cancer therapy and post-surgical skin regeneration. Herein, we report a multifunctional branched bioactive Si-Ca-P-Mo glass-ceramic nanoparticle (BBGN) with inlaid molybdate nanocrystals for an effective post-surgical melanoma therapy or infection therapy and defected skin reconstruction. Mixed-valence molybdenum (Mo4+ and Mo6+) doped BBGN (BBGN-Mo) was first synthesized via a hydrothermally assisted classical synthesis of BGN, which enables the structure with a lot of free electrons and oxygen vacancies. The BBGN-Mo exhibits excellent photothermal, antibacterial, enzyme-like radical scavenging, and anti-inflammatory as well as promoted vascularized efficiencies. BBGN-Mo could kill drug-resistant methicillin-resistant Staphylococcus aureus (MRSA) bacteria in vitro (99.5%) and in vivo (97.0%) at a low photothermal temperature (42 °C) and efficiently enhance the MRSA-infected wound repair. Additionally, BBGN-Mo could effectively inhibit tumor recurrence (96.4%), continuously improve the wound anti-inflammation and vascularization microenvironment, and significantly promote the post-surgical skin regeneration. This work suggests that conventional bioceramics could be turned to the highly efficient nanodrug for treating the challenge of post-surgical cancer therapy or infection therapy and tissue regeneration, through the mixed-valence strategy.

A Multifunctional Bioactive Glass-Ceramic Nanodrug for Post-Surgical Infection/Cancer Therapy-Tissue Regeneration.

NIR-triggerable ROS-responsive cluster-bomb-like nanoplatform for enhanced tumor penetration, phototherapy efficiency and antitumor immunity

The efficacy of immune checkpoint inhibition in inducing death of cancer cells is affected by the immunosuppressive "cold" tumor microenvironment, which results in a poor response by the patient's antitumor immune system. However, the immunomodulatory effects of immunogenic cell death in response to irritation by heat energy and reactive oxygen species (ROS) can switch the tumor microenvironment from "cold" to "hot." This study has developed a nanoadjuvant for immune therapy using iron tungsten oxide (FeWOx)-based nanosheets with surface PEGylation (FeWOx-PEG). This FeWOx-PEG nanoadjuvant serves as a chemodynamic reagent via the Fenton reaction and acts as a photosensitizer for photodynamic and photothermal therapy under near-infrared II laser irradiation; however, it could also be used to augment tumor-infiltrating T-cells and provoke a systemic antitumor immune response by combining the immunogenic cell death triggered by ROS and photothermal therapy with the immune checkpoint blockade. This research demonstrates that application of the FeWOx-PEG nanoadjuvant under the guidance of magnetic resonance/computed tomography/photoacoustic imaging can eliminate the primary tumor and suppress the growth of distant tumors.

Near-Infrared II Nanoadjuvant-Mediated Chemodynamic, Photodynamic, and Photothermal Therapy Combines Immunogenic Cell Death with PD-L1 Blockade to Enhance Antitumor Immunity.

https://doi.org/10.1016/j.apsb.2022.11.001

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

Sonodynamic therapy (SDT) and photothermal therapy (PTT) are two effective strategies for the treatment of atherosclerotic plaques. However, the low yield of reactive oxygen species (ROS) of conventional organic sonosensitizers and the low biosafety of hyperthermia limit the therapeutic efficacy of SDT and PTT. Herein, we report copper sulfide/titanium oxide heterostructure nanosheets modified with hyaluronic acid (HA) and PEG (HA-HNSs) for low-intensity sonodynamic and mild-photothermal synergistic therapy for early atherosclerotic plaques. CuS/TiO2 heterostructure nanosheets (HNSs) show high electron-hole separation efficiency and superior sonodynamic performance, because it has high surface energy crystal facets as well as a narrow band. Moreover, HNSs exhibit intense absorbance in the NIR-II region, which endows the nanosheets with excellent photothermal performance. With a further modification of HA, HA-HNSs can selectively target intraplaque proinflammatory macrophages through CD44-HA interaction. Because SDT reduces the expression of heat shock protein 90 and PTT facilitates the sonocatalytic process, the combination of SDT and PTT based on HA-HNSs could synergistically induce proinflammatory macrophage apoptosis. More importantly, the synergistic therapy prevents the progression of early atherosclerotic plaque by removing lesional macrophages and mitigating inflammation. Taken together, this work provides a macrophage-targeting sonodynamic/photothermal synergistic therapy, which is an effective translational clinical intervention for early atherosclerotic plaques.

Macrophage-Targeted Sonodynamic/Photothermal Synergistic Therapy for Preventing Atherosclerotic Plaque Progression Using CuS/TiO2 Heterostructured Nanosheets.

Engineering oxygen-deficient ZrO2-x nanoplatform as therapy-activated “immunogenic cell death (ICD)” inducer to synergize photothermal-augmented sonodynamic tumor elimination in NIR-II biological window

Lihong Sun

Papers

Engineering oxygen-deficient ZrO2-x nanoplatform as therapy-activated “immunogenic cell death (ICD)” inducer to synergize photothermal-augmented sonodynamic tumor elimination in NIR-II biological window