Xianwei Meng

Microwave thermotherapy, as an effective physical therapy for solid tumors, often leads to treatment resistance due to limitations such as hypoxia and abnormal blood vessels, resulting in tumor residue, metastasis, and recurrence. This study constructed a microwave‐responsive multifunctional nanocomposite (CCGM NCs). Using cobalt‐gallium (Co‐Ga) nanosheets as carriers, NO donor S‐nitrosocysteine is loaded, and temperature‐controlled material L‐menthol is coated to form a synergistic delivery system with thermal switch characteristics. Under microwave radiation, the material simultaneously achieves three functions: acting as a microwave sensitizer to generate local thermotherapy. Catalytic generation of O ₂ from hydrogen peroxide decomposition within the tumor and release of NO through microwave irradiation. The synergistic effect of O ₂ and NO inside the tumor not only alleviates hypoxia and improves vascular function, but also generates peroxynitrite anions, which work together with thermotherapy and reactive nitrogen species to enhance tumor killing. This system can effectively induce immunogenic cell death and initiate systemic anti‐tumor immune responses. Through the validation of bilateral tumor models and lung metastasis models, this strategy can efficiently ablate in situ tumors while stimulating significant distal tumor suppression and immune memory effects, effectively inhibiting tumor metastasis and recurrence.

Microwave (MW) ablation is a minimally invasive and efficient therapy for patients with breast cancer who are refractory to conventional treatments. However, incomplete ablation and the immunosuppressive tumor microenvironment (TME) often lead to tumor recurrence and metastasis. Herein, we report a sodium chloride‐based in situ tumor vaccine (NaCl@Fe/Al‐LDH@L‐Menthol, NLLM ISTVs) designed to enhance MW‐metalloimmunotherapy by amplifying ablation‐induced adaptive immunity. Upon intravenous administration, MW irradiation turns on the thermal response switch of L‐Menthol, which facilitates on‐demand in situ release of NaCl from NLLM ISTVs. Subsequently, the high concentrations of Na ⁺ /Cl ⁻ induce severe oxidative stress and Ca ²⁺ retention in tumor cells. Importantly, NLLM ISTVs combined with MW not only eradicates cancer cells but also induces potent apoptotic cell death, thereby generating robust immunogenic cell death (ICD) signals for boosting adaptive immunity. In vivo studies using primary, distant, and lung‐metastatic tumor models demonstrate potent suppression of tumor growth and metastasis with minimal systemic toxicity. These results highlight the dual action of NLLM ISTVs in direct tumor ablation and systemic immune activation, offering a promising strategy for clinical translation. This work provides a proof‐of‐concept for combining ion‐mediated metalloimmunotherapy with MW ablation to achieve robust systemic antitumor immunity.

Hepatocellular carcinoma (HCC) recurrence following microwave ablation poses a pressing clinical challenge, driven by metabolically adapted residual cells that establish an immunosuppressive tumour microenvironment. Our study identifies the post-ablation upregulation of fumarylacetoacetate hydrolase (FAH) as a crucial "metabolic checkpoint" promoting relapse. Elevated FAH expression results in increased fumarate levels within residual HCC cells, supporting tumour cell survival by enhancing energy metabolism while concurrently impairing CD8⁺ T cell function. Mechanistically, fumarate binds to and stabilises heat shock protein 70 (HSP70), establishing a thermal ablation induced FAH-fumarate-HSP70 axis that drives immunosuppression. To counteract this pivotal axis, we engineered a gallium-based functionalized nanoplatform. This system incorporates a lactate oxidase shell that responds to the lactate-rich tumour microenvironment, enabling the site-specific co-release of Ga³⁺, FAH-silencing plasmids and the glycolysis inhibitor 2-deoxy-D-glucose. Our nanoplatforms disrupt the FAH-fumarate-HSP70 axis to eradicate residual HCC, activate CD8⁺ T cells, and restore immunity, targeting recurrence dysregulation while integrating metabolic blockade with immunomodulation to prevent post-ablation relapse with clinical translation potential.

Microwave ablation (MWA) has emerged as one of the preferred modalities for treating hepatocellular carcinoma (HCC). However, its therapeutic efficiency is restricted by lactate accumulation after MWA. Lactate serves as a metabolic fuel for residual tumor cells, as well as acidifies the tumor microenvironment (TME) and impairs immune function, thereby fostering tumor recurrence and metastatic dissemination. Herein, we designed a dual-transformation strategy that turns metabolic fuel into metabolic burden and immunosuppressive pressure into power, implemented via bimetallic MOF-based nanoplatform (Dis@MgGa-MOF@TD/FA, DMGTF NCs), to counteract microwave-induced lactate elevation, reactivate immune activity and suppress primary tumor growth and metastatic progression. Specifically, after intravenous administration, folic acid (FA)-modified DMGTF accumulates in HCC, where microwave irradiation opens the 1-Tetradecanol (TD) gate to release diclofenac sodium (Dis). The released Dis suppresses MCT4-mediated lactate efflux, thereby disrupting lactate-driven energy supply and reshaping the TME. Meanwhile, microwave-activated DMGTF generates abundant ROS to impair mitochondrial lactate oxidation, thereby promoting intracellular lactate accumulation and inducing metabolic stress. Moreover, framework-derived Mg²⁺ restarts T cells, boosts proliferation, and augments IFN-γ secretion, converting immunosuppressive "pressure" into antitumor "power". As a result, DMGTF NCs combined with MW achieve excellent therapeutic effects in a model of hepatocellular carcinoma and lung metastasis. This MOF-based dual-transformation strategy provides a promising solution to the long-standing challenge of post-MWA tumor relapse and dissemination, offering new insights into the effective control of liver cancer.

Enhancing carrier separation efficiency in thermoelectric materials and enabling their directional movement via Schottky engineering to boost ROS generation.

Although heat can enhance the immunogenicity of tumors, inhomogeneous temperature distribution in deep-seated regions often leads to insufficient thermal exposure, resulting in limited antigen release and low immunogenicity. Herein, we designed microwave-sensitizing nanomotors that activate propulsion to break through biological barriers and the deep-seated delivery of heat and immune adjuvants to activate the immune response. Specifically, this nanomotor features a core of dendritic silica (DS) asymmetrically modified with bovine serum albumin-stabilized manganese dioxide nanoparticles (MnO₂@BSA) to form the DMB structure. Subsequently, the immune adjuvant R837 and tetradecanol were loaded to obtain the final microwave-sensitizing nanomotors, DMBR. Oxygen (O₂) bubbles generated from the catalytic decomposition of H₂O₂ by the heterostructured MnO₂@BSA propel the nanomotors to actively break through these biological barriers autonomously toward deep-seated tumor cells. Furthermore, microwave irradiation accelerates the production of O₂ bubbles, enhancing the nanomotor's movement efficiency. In vitro and in vivo studies demonstrated a 3-fold improvement of DMB. Moreover, the DMBR nanomotors promote the enhancement of heat dissemination, R837 delivery efficiency, and localized release of O₂ into deep tumor areas. Consequently, a robust immune response is triggered, as evidenced by an increased level of T cell infiltration, leading to significant suppression of both primary and distant tumors. This work presents a sequential barrier-overcoming nanomotor strategy for effective microwave thermal immunotherapy.

Dynamic therapy has gained increasing attention in the biomedical field due to its high therapeutic efficiency, low cytotoxicity and broad applicability. Nanoengineering sensitizers can enhance the antitumor efficacy of dynamic therapy through multiple aspects. This review comprehensively summarizes nanoengineering for enhancement of dynamic therapy. First, we discusse nanoengineering strategies for boosting the performance of different type dynamic sensitizers based on their activation mechanism. We then discuss strategies to address the cross‐cutting concerns across dynamic therapies. These strategies include enhancing tumor‐specific accumulation of sensitizers, modulating tumor microenvironment and optimizing reactive oxygen species (ROS)‐mediated tumoricidal effects. Subsequently, we also discuss the challenges faced by current design of dynamic sensitizers, including poorly understood mechanisms and challenges in large‐scale manufacturing. Moreover, discussion is provided on emerging artificial intelligence‐enabled strategies for next‐generation sensitizers preparation. This review aims to provide an valuable reference for research scientists, thereby facilitating the development of novel dynamic sensitizers.