Vaccines that are reliable and efficacious are essential in the fight against the COVID-19 pandemic. In this study, we designed a dual-adjuvant system with two pathogen-associated molecular patterns (PAMPs), MnO_x and CpG. This system can improve the retention of antigens at the injection site, facilitate pro-inflammatory cytokines secretion, further recruit and activate dendritic cells (DCs). As a result, antigens can be delivered to lymph nodes specifically, and adaptive immunity was strengthened. The immunized group showed an enhanced and broadened humoral and cellular immune response in systemic immunity and lung protection when combined with a tandem repeat-linked dimeric antigen version of the SARS-CoV-2 receptor binding domain (RBD_dimer). Remarkably, even with a significant reduction in antigen dosage (three times lower) and a decrease in injection frequencies, our nanovaccine was able to produce the highest neutralizing antibody titers against various mutants. These titers were four-fold higher for the wild-type strain and two-fold higher for both the Beta and Omicron variants in comparison with those elicited by the Alum adjuvant group. In conclusion, our dual-adjuvant formulation presents a promising protein subunit-based candidate vaccine against SARS-CoV-2.

With research burgeoning in nanoscience and nanotechnology, there is an urgent need to develop new biological models that can simulate native structure, function, and genetic properties of tissues to evaluate the adverse or beneficial effects of nanomaterials on a host. Among the current biological models, three-dimensional (3D) organoids have developed as powerful tools in the study of nanomaterial–biology (nano–bio) interactions, since these models can overcome many of the limitations of cell and animal models. A deep understanding of organoid techniques will facilitate the development of more efficient nanomedicines and further the fields of tissue engineering and personalized medicine. Herein, we summarize the recent progress in intestinal organoids culture systems with a focus on our understanding of the nature and influencing factors of intestinal organoid growth. We also discuss biomimetic extracellular matrices (ECMs) coupled with nanotechnology. In particular, we analyze the application prospects for intestinal organoids in investigating nano–intestine interactions. By integrating nanotechnology and organoid technology, this recently developed model will fill the gaps left due to the deficiencies of traditional cell and animal models, thus accelerating both our understanding of intestine-related nanotoxicity and the development of nanomedicines.

Multifunctional core–shell nanostructures formed by integration of distinct components have received wide attention as promising biological platforms in recent years. In this work, crystalline zeolitic imidazolate framework-8 (ZIF-8), a typical metal-organic framework (MOF), is coated onto single gold nanorod(AuNR) core for successful realization of synergistic photothermal and chemotherapy triggered by near-infrared (NIR) light. Impressively, high doxorubicin hydrochloride (DOX) loading capacity followed by pH and NIR light dual stimuli-responsive DOX release can be easily implemented through formation and breakage of coordination bonds in the system. Moreover, under NIR laser irradiation at 808 nm, these novel AuNR@MOF core–shell nanostructures exhibit effective synergistic chemo-photothermal therapy both in vitro and in vivo, confirmed by cell treatment and tumor ablation via intravenous injection.

Platinum nanoparticles (NPs) are reported to mimic various antioxidant enzymes and thus may produce a positive biological effect by reducing reactive oxygen species (ROS) levels. In this manuscript, we report Pt NPs as an enzyme mimic of ferroxidase by depositing platinum nanodots on gold nanorods (Au@Pt NDRs). Au@Pt NDRs show pH-dependent ferroxidase-like activity and have higher activity at neutral pH values. Cytotoxicity results with human cell lines (lung adenocarcinoma A549 and normal bronchial epithelial cell line HBE) show that Au@Pt NDRs are taken up into cells via endocytosis and translocate into the endosome/lysosome. Au@Pt NDRs have good biocompatibility at NDR particle concentrations lower than 0.15 nΜ. However, in the presence of H₂O₂, lysosomelocated NDRs exhibit peroxidase-like activity and therefore increase cytotoxicity. In the presence of Fe²⁺, the ferroxidase-like activity of the NDRs protects cells from oxidative stress by consuming H₂O₂. Thorough consideration should be given to this behavior when employing Au@Pt NDRs in biological systems.

Thermosensitive drug delivery systems (DDSs) face major challenges, such as remote and repeatable control of in vivo temperature, although these can increase the therapeutic efficacy of drugs. To address this issue, we coated near-infrared (NIR) photothermal Cu_1.75S nanocrystals with pH/thermos-sensitive polymer by in situ polymerization. The doxorubicine (DOX) loading content was up to 40 wt.%, with less than 8.2 wt.% of DOX being leaked under normal physiological conditions (pH = 7.4, 37 ℃) for almost 48 h in the absence of NIR light. These nanocapsules demonstrate excellent photothermal stability by continuous longterm NIR irradiation. Based on the stable and high photothermal efficiency (55.8%), pre-loaded drugs were released as desired using 808-nm light as a trigger. Both in vitro and in vivo antitumor therapy results demonstrated that this smart nanoplatform is an effective agent for synergistic hyperthermia-based chemotherapy of cancer, demonstrating remote and noninvasive control.