Qi Chen

Ischemic stroke, a leading cause of global mortality and disability, faces therapeutic limitations due to the narrow time window and restricted efficacy of current interventions such as thrombolysis and thrombectomy.

The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity, oxidative stress, inflammatory responses, and blood–brain barrier disruption. While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success, reperfusion injury remains a significant contributor to the exacerbation of brain injury. This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury. The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke, covering research progress in nanoparticle-based drug delivery, targeted therapy, and antioxidant and anti-inflammatory applications. Nano-based drug delivery systems offer several advantages compared to traditional therapies, including enhanced blood–brain barrier penetration, prolonged drug circulation time, improved drug stability, and targeted delivery. For example, inorganic nanoparticles, such as those based on CeO ₂ , have been widely studied for their strong antioxidant capabilities. Biomimetic nanoparticles, such as those coated with cell membranes, have garnered significant attention owing to their excellent biocompatibility and targeting abilities. Nanoparticles can be used to deliver a wide range of neuroprotective agents, such as antioxidants (e.g., edaravone), anti-inflammatory drugs (e.g., curcumin), and neurotrophic factors. Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions. Although nanotechnology has demonstrated great potential in animal studies, its clinical application still faces several challenges, including the long-term safety of nanoparticles, the feasibility of large-scale production, quality control, and the ability to predict therapeutic effects in humans. In summary, nanotechnology holds significant promise for the treatment of ischemic stroke. Future research should focus on further exploring the mechanisms of action of nanoparticles, developing multifunctional nanoparticles, and validating their safety and efficacy through rigorous clinical trials. Moreover, interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.

Signal transducer and activator of transcription 3 (STAT3) is widely recognized as an attractive target for cancer therapy due to its significant role in the initiation and progression of tumorigenesis. However, existing STAT3 inhibitors have suffered from drawbacks including poor efficacy, limited specificity, and undesirable off-target effects, due to the challenging nature of identifying active sites or allosteric regulatory pockets on STAT3 amenable to small-molecule inhibition. In response to these obstacles, we utilize the innovative proteolysis targeting chimera (PROTAC) technology to create a highly specific decoy-targeted protein degradation system for STAT3 protein, termed D-PROTAC. This system fuses DNA decoy that targets STAT3 with an E3 ligase ligand, utilizing a click chemistry approach. Experimental results demonstrate that D-PROTAC efficiently mediates the degradation of the STAT3 protein across various cancer cell types, leading to the downregulation of crucial downstream STAT3 targets, inhibiting tumor cell growth, triggering cell cycle arrest and apoptosis, and suppressing tumor immune evasion. Furthermore, D-PROTAC is capable of achieving significant tumor suppression in xenograft models. Overall, our research validates that D-PROTAC can successfully target and eliminate the “undruggable” STAT3, showcasing specificity and potent antitumor effects. This strategy will suggest a promising avenue for the development of targeted therapies against the critical functions of STAT3 in human cancers and potentially other diseases.

Cyclodextrins (CDs) are ubiquitous excipients, constituted of cyclic glucopyranose units, and possess a unique dual nature, that of a hydrophobic interior and a hydrophilic exterior. This enables their interaction with lipid-affinitive compounds and hydrophilic compounds, thereby augmenting their application in pharmaceutical formulations as agents for improving solubility, as well as fundamental elements of advanced drug delivery systems. Additionally, CDs, upon suitable modification, can strategically participate in the interaction with cellular components and physical barriers, such as the blood–brain barrier, where their intricate and multifunctional engagement leads to various biological impacts. This review consolidates the crucial features of CDs and their derivatives, and summarizes the applications of them as drug delivery systems in neurodegenerative disorders, emphasizing their notable potentials.

Glioma is the most common primary intracranial tumor, which is formed by the malignant transformation of glial cells in the brain and spinal cord. It has the characteristics of high incidence, high recurrence rate, high mortality and low cure rate. The treatments for glioma include surgical removal, chemotherapy and radiotherapy. Due to the obstruction of the biological barrier of brain tissue, it is difficult to achieve the desired therapeutic effects. To address the limitations imposed by the brain’s natural barriers and enhance the treatment efficacy, researchers have effectively used brain-targeted drug delivery systems (DDSs) in glioma therapy. Polyamidoamine (PAMAM) dendrimers, as branched macromolecular architectures, represent promising candidates for studies in glioma therapy. This review focuses on PAMAM-based DDSs in the treatment of glioma, highlighting their physicochemical characteristics, structural properties as well as an overview of the toxicity and safety profiles.