Iron oxide nanoparticles (IONPs) demonstrate substantial translational potential in precision medicine, leveraging their favourable biocompatibility and distinctive magnetic properties. This comprehensive review systematically analyses their established clinical applications including magnetic resonance imaging (MRI) contrast enhancement, oncological interventions, and iron deficiency therapies. It further examines the critical design parameters governing the performance, safety, and metabolic fate of IONPs from a clinical-translational perspective. It addresses pivotal challenges in their clinical application and translation, including synthetic reproducibility, scalable manufacturing, and long-term biosafety, while also reviewing recent promising advances aimed at overcoming these hurdles. Furthermore, the translational potential of emerging preclinical innovations, including magnetic particle imaging (MPI), stem cell tracking modalities, and novel oral iron supplementation approaches, was critically evaluated. When integrated with multimodal imaging platforms and personalized therapeutic regimens, these advancements would pave the way for IONPs to become transformative agents in next-generation precision medicine.

Noise-induced hearing loss (NIHL) is a highly prevalent form of sensorineural hearing damage that has significant negative effects on individuals of all ages and there are no effective drugs approved by the US Food and Drug Administration. In this study, we unveil the potential of superparamagnetic iron oxide nanoparticle assembly (SPIOCA) to reshape the dysbiosis of gut microbiota for treating NIHL. This modulation inhibits intestinal inflammation and oxidative stress responses, protecting the integrity of the intestinal barrier. Consequently, it reduces the transportation of pathogens and inflammatory factors from the bloodstream to the cochlea. Additionally, gut microbiota-modulated SPIOCA-induced metabolic reprogramming in the gut–inner ear axis mainly depends on the regulation of the sphingolipid metabolic pathway, which further contributes to the restoration of hearing function. Our study confirms the role of the microbiota–gut–inner ear axis in NIHL and provides a novel alternative for the treatment of NIHL and other microbiota dysbiosis-related diseases.

Acute lung injury (ALI) is a critical pulmonary condition characterized by high morbidity and mortality rates. Recent studies have highlighted the therapeutic potential of engineered exosomes derived from mesenchymal stem cell (MSC) in modulating the inflammatory response in ALI. Here, a novel approach was developed to fabricate engineered bone mesenchymal stem cells (BMSCs) derived exosomes by utilizing superparamagnetic iron oxide nanoparticles (SPIONs) and an alternating magnetic field (AMF) to precondition BMSCs. This study evaluated and compared the therapeutic potential of different groups of engineered exosomes in ALI mice model and analyzed their underlying mechanisms using high-throughput sequencing. BMSCs were isolated from SD rats and subjected to treatment with SPIONs and/or an AMF. Following this, we established a lipopolysaccharide (LPS)-induced ALI mice model and evaluated the therapeutic efficacy of exosomes from different groups by administering them via tail vein injection. The expression profiles of microRNAs (miRNAs) in exosomes were compared to explore the mechanism of regulating inflammatory response and ameliorating lung injury. 25 µg/mL SPIONs and 3mT AMF were the best conditions for preparing engineered exosomes, which reduced the level of pro-inflammatory factors and had the most significant effect in repaired lung damage in vivo. The transfection of miR-145-5p mimics enhanced Bronchial Epithelium transformed with Ad12-SV40 2B (BEAS-2B) cells viability and reduced relevant inflammation expression in vitro experiments. The engineered exosomes obtained by low dose SPIONs combined with AMF can help regulate the level of inflammatory factors and improve lung injury. Targeted regulation of kruppel-like factor 5 (KLF5) by exosomal miR-145-5p and inhibition of the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway play a key role in this vitro process.

The low tumor permeability of nanomedicines is a major challenge for their application in tumor therapy. Reducing the size of nanomedicines or integrating penetrating peptides has been demonstrated to be very helpful to improve the tumor permeability of nanomedicines. In this paper, poly(amidoamine) (PAMAM) functionalized with the penetrating peptide CRGDK was designed as a drug carrier with a diameter of ∼5 nm. Paclitaxel (PTX) was used as a model drug and covalently linked to the carrier via a biocleavable ester bond. The CRGDK-functionalized drug-loaded nanoparticle exhibited a higher cellular uptake and a higher tumor accumulation and penetration than its nontargeted counterpart, which also endowed the functionalized nanomedicine with a higher antitumor efficiency than its nontargeted counterpart and the clinical Taxol formulation. The good performance of the peptide-bearing PAMAM-based nanomedicine indicates that our strategy is feasible to improve the tumor accumulation and penetration of nanomedicines.