Most disposable plastic products are degraded slowly in the natural environment and continually turned to microplastics (MPs) and nanoplastics (NPs), posing additional environmental hazards. The toxicological assessment of MPs for marine organisms and mammals has been reported. Thus, there is an urgent need to be aware of the harm of MPs to the human immune system and more studies about immunological assessments. This review focuses on how MPs are produced and how they may interact with the environment and our body, particularly their immune responses and immunotoxicity. MPs can be taken up by cells, thus disrupting the intracellular signaling pathways, altering the immune homeostasis and finally causing damage to tissues and organs. The generation of reactive oxygen species is the mainly toxicological mechanisms after MP exposure, which may further induce the production of danger-associated molecular patterns (DAMPs) and associate with the processes of toll-like receptors (TLRs) disruption, cytokine production, and inflammatory responses in immune cells. MPs effectively interact with cell membranes or intracellular proteins to form a protein-corona, and combine with external pollutants, chemicals, and pathogens to induce greater toxicity and strong adverse effects. A comprehensive research on the immunotoxicity effects and mechanisms of MPs, including various chemical compositions, shapes, sizes, combined exposure and concentrations, is worth to be studied. Therefore, it is urgently needed to further elucidate the immunological hazards and risks of humans that exposed to MPs.

The study of toxicity and potential risks of engineered nanoparticles is of particular importance in nanomedicine. Endotoxin, a common contaminant of bacterial origin, has biological effects that can mask the true biological effects of nanoparticles, if its presence is overlooked. In this review, we report the features of nanoparticle contamination by endotoxin, and the different biological effects of endotoxin-contaminated nanoparticles. We will describe different methods for endotoxin detection applied to nanoparticles, and discuss their pros and cons. Eventually, we describe various methods for eliminating endotoxin contamination in nanoparticles. Although there is no universal technique for efficiently removing endotoxin from nanoparticles, specific solutions can be found case by case, which can allow us to perform nanosafety studies in biologically relevant conditions.

Due to the existence of considerable quantities of metallic and carbonaceous impurities, the key factor and mechanism for the reported toxicity of carbon nanotubes (CNTs) are unclear. Here, we first quantify the contribution of metal residues and fiber structure to the toxicity of CNTs. Significant quantities of metal particles could be mobilized from CNTs into surrounding fluids, depending on the properties and constituents of the biological microenvironment, as well as the properties of metal particles. Furthermore, electron spin resonance measurements confirm that hydroxyl radicals can be generated by both CNTs containing metal impurities and acid-leachable metals from CNTs. Several biomolecules facilitate the generation of free radicals, which might be due to the participation of these biomolecules in redox cycling influenced by pH. Among several major metal residues, Fe has a critical role in generating hydroxyl radicals, reducing cell viability and promoting intracellular reactive oxidative species. Cell viability is highly dependent on the amount of metal residues and iron in particular, but not tube structure, while the negative effect of CNTs themselves on cell viability is very limited in a certain concentration range below 80 μg ml⁻¹. It is crucial to systematically understand how these exogenous and endogenous factors influence the toxicity of CNTs to avoid their undesirable toxicity.

Cancers are composed of heterogeneous subpopulations with various tumor-initiating capacities, yet key stem cell genes associated with enhanced tumor-initiating capacities and their regulatory mechanisms remain elusive. Here, we analyzed patient-derived xenografts from melanoma, colon, and pancreatic cancer tissues and identified enrichment of tumor-initiating cells in MHC class I-hi cells, where CDK1, a master regulator of the cell cycle, was upregulated. Overexpression of CDK1, but not its kinase-dead variant, in melanoma cells increased their spheroid forming ability, tumorigenic potential, and tumor-initiating capacity; inhibition of CDK1 with pharmacologic agents reduced these characteristics, which was unexplained by the role of CDK1 in regulating the cell cycle. Proteomic analysis revealed an interaction between CDK1 and the pluripotent stem cell transcription factor Sox2. Blockade or knockdown of CDK1 resulted in reduced phosphorylation, nuclear localization, and transcriptional activity of Sox2. Knockout of Sox2 in CDK1-overexpressing cells reduced CDK1-driven tumor-initiating capacity substantially. Furthermore, GSEA analysis of CDK1hi tumor cells identified a pathway signature common in all three cancer types, including E2F, G2M, MYC, and spermatogenesis, confirming a stem-like nature of CDK1hi tumor cells. These findings reveal a previously unrecognized role for CDK1 in regulating tumor-initiating capacity in melanoma and suggest a novel treatment strategy in cancer via interruption of CDK1 function and its protein-protein interactions. Significance: These findings uncover CDK1 as a new regulator of Sox2 during tumor initiation and implicate the CDK1–Sox2 interaction as a potential therapeutic target in cancer.