Shuanghu Wang

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with limited treatment options and poor prognosis due to the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Doxorubicin (DOX)-based chemotherapy remains the standard of care, yet dose-limiting cardiotoxicity and rapid chemoresistance compromise efficacy. To overcome these hurdles, we engineered rotating magnetic field-driven nanorobots (MFDNs) comprising DOX-loaded hollow mesoporous iron oxide nanoparticles cloaked with 4T1 cancer cell membranes. Under a rotating magnetic field (RMF; 5 Hz, 100 mT), MFDNs self-assemble into dynamic chains, evading the aggregation that plagues static magnetic field approaches and enabling deep intratumoral penetration. This dual-targeting mechanism, passive homing via membrane recognition and active navigation via RMF, delivers a three-fold higher intracellular DOX concentration than uncoated carriers. Mechanistically, MFDNs depleted intracellular glutathione by 70%, suppressed glutathione peroxidase-4 (GPX4), and elevated Fe ²⁺ , reactive oxygen species (ROS), and lipid peroxidation, thereby triggering robust ferroptosis. In 4T1 tumor-bearing mice, intravenous MFDNs plus RMF shrank tumors by 90% compared with 45% for free DOX, without systemic toxicity or weight loss. Histopathology confirmed extensive necrosis, abundant ferroptosis markers, and negligible off-target accumulation. Collectively, the seamless integration of dynamic RMF guidance with biomimetic membrane cloaking positions MFDNs as a clinically translatable nanoplatform that overcomes chemoresistance and markedly improves therapeutic outcomes for TNBC.

Purpose: The main purpose of the present study was to explore chitosan as a polymeric material for the preparation of vonoprazan nanoparticles intended for use as a delivery system for acid-related diseases. Methods: Vonoprazan-loaded chitosan nanoparticles were formulated using the ionotropic gelation method and characterized in terms of size, zeta potential, polydispersity index, drug entrapment efficiency (EE), FTIR, XRD, Thermal analysis, SEM, in vitro release study at two different pH levels, and drug release kinetics. Acute oral toxicity was assessed to evaluate safety and pharmacokinetic studies were performed to determine bioavailability. Results: The optimized formulation VCHNP4 demonstrated a mean particle size of 496.5± 1.19 nm, a zeta potential of 25.4± 3.07 mV, a polydispersity index of 0.474± 1.97, and an entrapment efficiency of 78.09± 0.41. Surface morphology studies revealed a spherical shape with inclusions of drug-loaded chitosan nanoparticles. Thermal stability was improved, as observed by thermal analysis, and PXRD confirmed the amorphous state of the drug. Saturation solubility testing indicated significantly enhanced solubility of the drug and exhibited pH-dependent drug release, with higher release at pH 1.2 compared to pH 6.8, following the Korsmeyer-Peppas model. Acute oral toxicity studies showed no major differences in the clinical parameters between the control and treatment groups. In vivo pharmacokinetics showed that VCHNPs achieved superior Cmax (307 ± 0.61 ng/mL) compared to VPZ (41 ± 1.01 ng/mL) (p < 0.05). Conclusions: This study showed that mucoadhesive polymeric nanoparticles of vonoprazan significantly enhanced solubility, pH-dependent release, and improved mucoadhesion, making it a promising approach to improve the oral bioavailability of drugs with poor water solubility.

Spinal cord injury (SCI) remains a major clinical challenge because the inflammatory and oxidative microenvironment drives secondary tissue damage. Although mollugin (Mol) possesses anti‐inflammatory, antioxidant, and neuroprotective activities, its therapeutic application is limited by poor water solubility and rapid clearance. In this study, we developed a RVG‐modified liposomal nanoplatform for targeted delivery of mollugin (Mol@Lip‐RVG) as a novel therapeutic strategy for SCI. The Mol@Lip‐RVG nanoplatform exhibited excellent biocompatibility, favorable physicochemical characteristics, and sustained drug release profile. In vitro studies demonstrated that Mol@Lip‐RVG effectively downregulated pro‐inflammatory mediators, promoted microglial polarization from the pro‐inflammatory M1 phenotype toward the anti‐inflammatory M2 phenotype, and significantly reduced reactive oxygen species production. In SCI mice, the RVG modification enabled efficient crossing of the BSCB and selective accumulation at the injury site through specific binding to nAChRs. This targeted delivery resulted in enhanced neuro‐preservation and substantial improvement in motor function recovery, achieved through dual modulation of microglial reprogramming and attenuation of oxidative stress. Mechanistically, we demonstrated that Mol@Lip‐RVG exerts its therapeutic effects is associated with inhibition of the NF‐κB signaling pathway, thereby suppressing neuroinflammation. Collectively, these findings establish the Mol@Lip‐RVG nanoplatform as a promising targeted therapeutic approach that addresses both the delivery challenges and complex pathophysiology of spinal cord injury.

Introduction: Cerebral ischemic stroke has high mortality and disability rates with limited targeted therapeutic strategies. Biomimetic nanocarriers can optimize drug delivery efficiency and exert neuroprotection effects, providing a promising strategy for ischemia-reperfusion injury treatment. Methods: Hollow mesoporous silica nanoparticles (HMSNs) were synthesized via an improved Stoer method and loaded with imperatorin (IMP). Subsequently, neutrophil cell membranes (NCM) extracted from DMSO-induced HL-60 cells were coated onto the nanoparticles to construct NCM/IMP@HMSNs. Nanomaterial characterization was carried out. In vitro oxygen-glucose deprivation/reoxygenation (OGD/R) models in SH-SY5Y cells and in vivo rat middle cerebral artery occlusion/reperfusion (MCAO/R) models were established to explore the underlying neuroprotective mechanisms. Results: The synthesized NCM/IMP@HMSNs nanoparticles possessed uniform particle size (~143 nm) and favorable stability, with an encapsulation efficiency of 31.84%. In vitro results revealed that IMP significantly increased the viability of OGD/R-injured SH-SY5Y cells compared with the model group. In vivo experiments showed that NCM/IMP@HMSNs efficiently accumulated in ischemic brain tissue, notably decreased mNSS scores, and reduced cerebral infarct volume by approximately 33.31% compared with the MCAO/R group. This nanosystem activated the Nrf2/ARE/Keap1 pathway, thereby upregulating HO-1 expression to strengthen antioxidant capacity, alleviate the accumulation of cerebral oxidative stress products, and regulate the activities of SOD, GSH, CAT and LDH. Conclusion: The biomimetic NCM/IMP@HMSNs nanoplatform enhances the neuroprotective efficacy against ischemia–reperfusion injury via activating the Nrf2/ARE/Keap1 pathway, offering a promising targeted therapeutic approach for ischemic stroke therapy.

Leukemia, a prevalent malignancy characterized by chromosomal aberrations, was targeted in this study to assess the anti-cancer potential of naturally isolated novel coumarins. Novel coumarins (isolated from the natural source Sterculia colorata) were assessed against HL-60 leukemia cells using in vitro and in silico approaches. The MTT assay demonstrated significant cytotoxicity of the compounds against HL-60 cells. Molecular docking studies revealed strong binding interactions with CDK-2 and BCL-2 proteins, supporting the in vitro results. Compound 2 exhibited the highest binding energy with CDK-2. Molecular dynamics simulations, binding free energy calculations, principal component analysis (PCA), and free energy landscape analyses were performed to assess the stability of the Compound 2-CDK-2 complex. The results indicated that the complex remained stable during the MD simulation with favorable binding free energies. ADMET predictions confirmed favorable pharmacokinetic profiles and safety from hERG blockade. These findings highlight the compounds’ promising pharmacological activity and potential for further drug development, though additional studies are needed to explore their clinical applications.

Background and Objective: Danshensu and atorvastatin are employed in the management of cardiovascular diseases (CVDs) to lower blood lipid levels and dilate blood vessels. Therefore, this study aimed to examine the potential pharmacokinetic interaction between danshensu and atorvastatin in rats. Materials and Methods: Chromatography was performed using a CORTECST UPLC C18 column (2.1 × 1.5 mm, 1.6 μm) at a temperature of 40 °C. Acetonitrile and water were combined in the mobile phase at a rate of 0.4 mL/min via gradient elution. The methodology was validated under the guidance of the FDA and EMA literature. A total of 12 Sprague-Dawley (SD) rats were randomly assigned into two groups: the experimental group (treated with 150 mg/kg/day danshensu) and the control group (treated with 0.5% CMC-Na). Atorvastatin 10 mg/kg was administered after two weeks. The proposed method meets all the standards of bioanalysis technology verification. Results: Compared to the control group, the experimental group exhibited significant differences in the area under the curve (AUC), t1/2, CLz/F, and Cmax (p < 0.05). The AUC, Cmax, and t1/2 of the experimental group were higher, yet the clearance rate was significantly slowed. Conclusions: This technique was effectively utilized to investigate the pharmacokinetic interaction between danshensu and atorvastatin in rats, which may be of significant clinical importance and contribute to the rationalization of clinical medicine, ultimately facilitating individualized administration.

Abdominal aortic aneurysms (AAAs) are life-threatening cardiovascular disorders with limited treatment options, largely due to an incomplete understanding of their molecular and cellular pathogenesis. A comprehensive elucidation of the mechanisms driving AAA initiation, progression, and rupture is critical for developing novel therapeutic interventions. Emerging research has highlighted the central role of inflammatory processes in AAA pathophysiology, including dysregulated extracellular matrix (ECM) remodeling, chronic vascular inflammation, immune cell infiltration, and vascular smooth muscle cell (VSMC) dysfunction. These pathological processes are regulated by complex signaling pathways with divergent roles in AAA progression: while NF-κB, MAPK, STAT, and Notch signaling exacerbate disease pathogenesis, AMPK, PPAR-γ, and Nrf2 pathways exert protective effects. Notably, the PI3K/Akt and TGF-β signaling cascades demonstrate context-dependent dual roles, capable of either promoting or inhibiting AAA development. This comprehensive review synthesizes current knowledge of AAA pathophysiology with emphasis on druggable targets within these signaling networks. We critically evaluate emerging therapeutic strategies including miRNA-based interventions, nanoparticle-mediated drug delivery systems, and stem cell therapies that offer promising approaches for precision modulation of disease-specific pathways. By integrating current mechanistic understanding with therapeutic development, this review aims to provide a framework for designing effective pharmacological strategies that could transform AAA management from surgical intervention to medical prevention, addressing a critical unmet clinical need.

Objective: Itraconazole (ITZ) is a BCS class II antifungal agent difficult to formulate due to its poor water solubility (< 0.2 mmol /mL) and variable oral bioavailability (~55%). This study aimed to develop Polycaprolactone (PCL) nanoparticles to improve their transdermal delivery. Methods: The nanoparticles were prepared using a modified nanoprecipitation method, resulting in ten formulations (F1 to F10). The optimized formulation (F2) was incorporated into a carbopol gel. Characterization included particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), and in vitro drug release at pH 5.5 and 7.4. Ex vivo permeation, skin irritation, and stability were also evaluated. Results: Formulation F2 (40 mg PCL, 2% Poloxamer 407 showed optimal properties: particle size of 154.6 nm, PDI (0.378), zeta potential (− 10.7 ± 5.36 mV), and EE (88.4 ± 1.2%). A pH-dependent sustained release was observed, with 80.41% and 94.34% cumulative release at pH 5.5 and 7.4 over 24 hours, respectively, following Higuchi kinetics (R²= 0.9804 at pH 5.5). The gel demonstrated significantly higher permeation (Q₂₄: 173.29 ± 3.12 μg/cm²; Jss: 7.22 ± 0.15 μg/cm²/h) versus plain gel (Q₂₄: 75.35 ± 1.35 μg/cm²; Jss: 3.11 ± 0.08 μg/cm²/h), with an enhancement ratio of 2.32. Characterization confirmed the amorphous state of ITZ and absence of interactions. The formulation was non-irritating (PII=0) and stable for three months. Conclusion: A promising and biocompatible PCL-based gel was successfully developed, providing an effective approach for enhanced transdermal delivery of ITZ through sustained drug release and improved skin permeability.