Nanobodies are the recombinant variable domains of heavy-chain-only antibodies, with many unique properties such as small size, excellent solubility, superior stability, quick clearance from blood, and deep tissue penetration. As a result, nanobodies have become a promising tool for the diagnosis and therapy of diseases. As imaging tracers, nanobodies allow an early acquisition of high-quality images, provide a comprehensive evaluation of the disease, and subsequently enable a personalized precision therapy. As therapeutic agents, nanobodies enable a targeted therapy by lesion-specific delivery of drugs and effector domains, thereby improving the specificity and efficacy of the therapy. Up to date, a wide variety of nanobodies have been developed for a broad range of molecular targets and have played a significant role in patients with a broad spectrum of diseases. In this review, we aim to outline the current state-of-the-art research on the nanobodies for medical applications and then discuss the challenges and strategies for their further clinical translation.

Pancreatic cancer is a deadly disease with little response to standard therapies. Irreversible electroporation (IRE) has emerged as a novel ablative technique for the clinical treatment of pancreatic cancer. Combinations of IRE and immunotherapies, including anti‐programmed death 1 (αPD1) immune checkpoint blockade, have shown promising efficacy in both preclinical and clinical studies. However, tumor recurrence remains an obstacle that needs to be overcome. It herein is shown that IRE induces a substantial infiltration of neutrophils into pancreatic tumors. These neutrophils are then polarized into a protumor phenotype by immunosuppressive cues, in particular transforming growth factor β (TGF‐β). Using glutathione‐responsive degradable mesoporous silica nanoparticles loaded with SB525334, an inhibitor of TGF‐β1 receptor, it is demonstrated that local inhibition of TGF‐β within the tumor microenvironment promotes neutrophil polarization into an antitumor phenotype, enhances pancreatic cancer response to combined IRE and αPD1 therapy, and induces long‐term antitumor memory. The therapeutic efficacy is also attributed to tumor infiltration by CD8⁺ cytotoxic T cells, depletion of regulatory T cells, and maturation of antigen‐presenting dendritic cells. Thus, modulating neutrophil polarization with nanomedicine is a promising strategy for treating pancreatic cancer.

Bacterial infections are the main infectious diseases and cause of death worldwide. Antibiotics are used to treat various infections ranging from minor to life-threatening ones. The dominant route to administer antibiotics is through oral delivery and subsequent gastrointestinal tract (GIT) absorption. However, the delivery efficiency is limited by many factors such as low drug solubility and/or permeability, gastrointestinal instability, and low antibacterial activity. Nanotechnology has emerged as a novel and efficient tool for targeting drug delivery, and a number of promising nanotherapeutic strategies have been widely explored to overcome these obstacles. In this review, we explore published studies to provide a comprehensive understanding of the recent progress in the area of orally deliverable nano-antibiotic formulations. The first part of this article discusses the functions and underlying mechanisms by which nanomedicines increase the oral absorption of antibiotics. The second part focuses on the classification of oral nano-antibiotics and summarizes the advantages, disadvantages and applications of nanoformulations including lipid, polymer, nanosuspension, carbon nanotubes and mesoporous silica nanoparticles in oral delivery of antibiotics. Lastly, the challenges and future perspective of oral nano-antibiotics for infection disease therapy are discussed. Overall, nanomedicines designed for oral drug delivery system have demonstrated the potential for the improvement and optimization of currently available antibiotic therapies.