Glioma is the most common malignant tumor of the central nervous system (CNS). Therapeutic efficacy of glioma treatment is greatly limited by the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB), which restrict the passage of most drugs into the brain and tumors. Developing drug delivery systems that cross the BBB and BBTB will aid in the treatment of glioma and malignant brain metastases. One emerging solution is to identify peptide vectors that penetrate the BBB/BBTB. Herein, a novel BBB/BBTB-penetrating peptide was identified from the phage-displayed peptide library. Peptide–drug conjugates (PDCs) were derived and applied to treat glioma and breast cancer brain metastases. Antitumor activity was achieved in both tumor models with synergistic effects when combined with the currently used chemotherapy drug temozolomide. The peptide reported herein can serve as a universal vector for shuttling compounds across the BBB; therefore, it may have wide applications for treating brain tumors and other CNS diseases.

Host defense systems can invade viral infection through immune responses and cellular metabolism. Recently, many studies have shown that cellular metabolism can be reprogrammed through N6‐methyladenosine (m6A) modifications during viral infection. Among of them, methyltransferase like‐14 enzyme (METTL14) plays an important role in m6A RNA modification, yet its antiviral function still remains unclear. In this work, it is uncovered that metal–protein nanoparticles designated GSTP1‐MT3(Fe2+) (MPNP) can polarize macrophages toward the M1 phenotype and activate immune responses to induce Interferon‐beta (IFN‐β) production in vesicular stomatitis virus (VSV)‐infected macrophages. Further investigation elucidates that a high dose of IFN‐β can promote the expression of METTL14, which has a well anti‐VSV capacity. Moreover, it is found that other negative‐sense single‐stranded RNA viruses, such as influenza viruses (H1N1(WSN)), can also be inhibited through either immune responses or METTL14. Collectively, these findings provide insights into the antiviral function of METTL14 and suggest that the manipulation of METTL14 may be a potential strategy to intervene with other negative‐sense single‐stranded RNA viruses infections.

Self‐assembled protein nanoparticles have attracted much attention in biomedicine because of their biocompatibility and biodegradability. Protein nanoparticles have become widely utilized as diagnostic or therapeutic agents for various cancers. However, there are no reports that protein nanoparticles can specifically target mitochondria. This targeting is desirable, since mitochondria are critical in the development of cancer cells. In this study, the discovery of a novel self‐assembled metal protein nanoparticle, designated GST‐MT‐3, is reported, which targets the mitochondria of cancer cells within 30 min in vitro and rapidly accumulates in tumors within 1 h in vivo. The nanoparticles chelate cobalt ions [GST‐MT‐3(Co2+)], which induces reactive oxygen species (ROS) production and reduces the mitochondrial membrane potential. These effects lead to antitumor activity in vivo. GST‐MT‐3(Co2+) with covalently conjugated paclitaxel synergistically suppress tumors and prolong survival. Importantly, the effective dosage of paclitaxel is 50‐fold lower than that utilized in standard chemotherapy (0.2 vs 10 mg kg−1). To the best of the authors' knowledge, GST‐MT‐3 is the first reported protein nanoparticle that targets mitochondria. It has the potential to be an excellent platform for combination therapies.