Cascade Catalytic Nanoparticles Selectively Alkalize Cancerous Lysosomes to Suppress Cancer Progression and Metastasis.

Lysosomes are critical in modulating the progression and metastasis for various cancers. There is currently an unmet need for lysosomal alkalizers that can selectively and safely alter the pH and inhibit the function of cancer lysosomes. Here an effective, selective, and safe lysosomal alkalizer is reported that can inhibit autophagy and suppress tumors in mice. The lysosomal alkalizer consists of an iron oxide core that generates hydroxyl radicals (•OH) in the presence of excessive H+ and hydrogen peroxide inside cancer lysosomes and cerium oxide satellites that capture and convert •OH into hydroxide ions. Alkalized lysosomes, which display impaired enzyme activity and autophagy, lead to cancer cell apoptosis. It is shown that the alkalizer effectively inhibits both local and systemic tumor growth and metastasis in mice. This work demonstrates that the intrinsic properties of nanoparticles can be harnessed to build effective lysosomal alkalizers that are both selective and safe.

Unraveling mitochondria-targeting reactive oxygen species modulation and their implementations in cancer therapy by nanomaterials.

Functional subcellular organelle mitochondria are emerging as a crucial player and driver of cancer. For maintaining the sites of cellular respiration, mitochondria experience production, and accumulation of reactive oxygen species (ROS) underlying oxidative damage in electron transport chain carriers. Precision medicine targeting mitochondria can change nutrient availability and redox homeostasis in cancer cells, which might represent a promising strategy for suppressing tumor growth. Herein, this review highlights how the modification capable of manipulating nanomaterials for ROS generation strategies can influence or compensate the state of mitochondrial redox homeostasis. We propose foresight to guide research and innovation with an overview of seminal work and discuss future challenges and our perspective on the commercialization of novel mitochondria-targeting agents.

Neutrophils: Driving inflammation during the development of hepatocellular carcinoma.

The relationship between immune and inflammatory responses in hepatocellular carcinoma (HCC) has garnered significant interest. In the peripheral blood and tumour microenvironment (TME), neutrophils, which are innate immune cells, crucially respond to various inflammatory factors, leading to tumour progression. To some extent, they affect the clinical treatment strategy and survival among HCC patients. A high circulating neutrophil-to-lymphocyte ratio is a reliable factor that can be used to predict poor outcomes in HCC patients. However, the mechanisms underlying the protumoural effects of circulating neutrophils remain poorly understood. Besides, the distinct role and function of neutrophils at the site of HCC remain relatively unclear, which is partially attributed to their substantial heterogeneity compared with other immune cells. In this review, we firstly discuss the current information available, detailing distinct subsets, functional phenotypes, and the impact of circulating and tumour-infiltrating neutrophils on tumourigenesis in HCC. Furthermore, we describe recent pre-clinical and clinical studies concerning neutrophils for evaluating the feasibility of targeting diverse protumoural aspects to improve therapeutic efficacy, thus paving the way for neutrophil-based treatment, especially in combination with immunotherapy.