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Germinal matrix hemorrhage (GMH) is a devasting neurological disease in premature newborns. After GMH, brain iron overload associated with hemoglobin degradation contributed to oxidative stress, causing disruption of the already vulnerable blood-brain barrier (BBB). Mitochondrial ferritin (FTMT), a novel mitochondrial outer membrane protein, is crucial in maintaining cellular iron homeostasis. We aimed to investigate the effect of FTMT upregulation on oxidative stress and BBB disruption associated with brain iron overload in rats. A total of 222 Sprague-Dawley neonatal rat pups (7 days old) were used to establish a collagenase-induced GMH model and an iron-overload model of intracerebral FeCl 2 injection. Deferiprone was administered via gastric lavage 1 h after GMH and given daily until euthanasia. FTMT CRISPR Knockout and adenovirus (Ad)-FTMT were administered intracerebroventricularly 48 h before GMH and FeCl 2 injection, respectively. Neurobehavioral tests, immunofluorescence, Western blot, Malondialdehyde measurement, and brain water content were performed to evaluate neurobehavior deficits, oxidative stress, and BBB disruption, respectively. The results demonstrated that brain expressions of iron exporter Ferroportin (FPN) and antioxidant glutathione peroxidase 4 (GPX4) as well as BBB tight junction proteins including Claudin-5 and Zona Occulta (ZO)-1 were found to be decreased at 72 h after GMH. FTMT agonist Deferiprone attenuated oxidative stress and preserved BBB tight junction proteins after GMH. These effects were partially reversed by FTMT CRISPR Knockout. Iron overload by FeCl 2 injection resulted in oxidative stress and BBB disruption, which were improved by Ad-FTMT mediated FTMT overexpression. Collectively, FTMT upregulation is neuroprotective against brain injury associated with iron overload. Deferiprone reduced oxidative stress and BBB disruption by maintaining cellular iron homeostasis partially by the upregulating of FTMT after GMH. Deferiprone may be an effective treatment for patients with GMH., Competing Interests: Declaration of competing interest All Authors declare that they have no competing financial interests or conflicts of interest in the current study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although the survival rate of hematological malignancies (HM) has increased in recent years, the unnecessary adverse effect to the body is usually generated by the traditional chemotherapy for HM due to the lack of specificity to tumor tissue. Nanodrug delivery systems have exhibited unique advantages in targetability, stability and reducing toxicity, attracting wide concern, which is expected to be the prevalent alternative for the treatment of HM. In this review, we systemically introduced the current therapeutic strategies and the categories of HM. Subsequently, five key factors including circulation, targeting, penetration, internalization and release involving in tailoring nanoparticles were demonstrated, followed by the introduction of the development of nanodrug delivery-traditional synthetic nanomaterilas, biomimetic cell membrane coating nanomaterials, cell-based nanomaterials as well as immunotherapy combined with nanodrug. Afterwards, the recent advances of nanodrug delivery system for the treatment of HM were introduced. Moreover, the challenge and prospect of nanodrug delivery system in treating HM were discussed. The promising drug delivery system will provide new therapeutic avenues for the treatment of HM., Competing Interests: Declaration of Competing Interest There are no conflicts to declare., (Copyright © 2022. Published by Elsevier Ltd.)