Doxorubicin (DOX) is a widely used first-line chemotherapeutic drug with potent anti-tumor activity, yet severe off-target cardiotoxicity and hepatotoxicity severely restrict its clinical application. This study aimed to construct an ultrasound-responsive PLGA microbubble delivery system to realize tumor-specific controlled DOX release under low-intensity focused ultrasound (US), integrate real-time ultrasonic tumor imaging, and simultaneously reduce systemic side effects of free DOX. DOX-loaded PLGA microbubbles (DOX-MBs) were fabricated and evaluated for ultrasound contrast enhancement and US-triggered intracellular DOX release. In vitro and in vivo experiments were performed to evaluate tumor cell apoptosis induction, anti-metastatic capacity, as well as cardiac and hepatic toxic side effects of this theranostic platform. The DOX-MB system enabled real-time ultrasound visualization of tumor lesions. US exposure disrupted the microbubbles and promoted intracellular DOX release. Compared with free DOX, this platform significantly elevated tumor cell apoptosis, suppressed tumor distant metastasis, and effectively alleviated DOX-induced cardiotoxicity and hepatotoxicity in vivo. The developed US-activated DOX-loaded PLGA microbubbles integrate diagnostic ultrasound imaging and tumor-targeted chemotherapy with reduced organ toxicity. This work provides a facile and novel design strategy for imaging-guided, ultrasound-triggered tumor theranostic microplatforms.
Multifunctional electrospun nanofibrous structures integrating bioactive Schiff base ligands and metal complexes by strategic design present a robust method for advancing next-generation therapeutic biomedical materials. The present work aims to functionalize poly(acrylonitrile-co-vinyl acetate) (PAN) nanofibers with a rhodamine-based Schiff base (FBO) and its copper(II) complex (CuFBO) by the technique of electrospinning. The resulted FBO/PAN and CuFBO/PAN nanofibers were fully characterized and assessed concerning their antioxidant, antidiabetic, antimicrobial, biofilm inhibition, DNA cleavage, and photo antimicrobial activities. DPPH assay demonstrated that PAN exhibited minimal radical-scavenging activity (<1%), whereas FBO/PAN significantly enhanced antioxidant performance, reaching 34.24% at 100 & micro;g/mL. Incorporation of Cu2+ into FBO/PAN slightly reduced antioxidant efficiency, likely due to donor site occupation. Antidiabetic activity evaluation revealed negligible inhibition for PAN, moderate improvement for FBO/PAN (up to 54.86%), and the highest activity for CuFBO/PAN (69.07% at 100 & micro;g/mL), indicating that Cu2+ ions coordination enhances enzyme inhibition. DNA cleavage assay confirmed that none of the composites induced strand breaks. Antimicrobial and anti-biofilm evaluations showed that FBO/PAN markedly suppressed microbial growth and biofilm formation in a concentration-dependent manner, with CuFBO/PAN exhibiting the strongest effects, achieving complete inhibition at higher concentrations. Photodynamic therapy (PDT) experiments demonstrated 100% microbial suppression for both FBO/PAN and CuFBO/PAN, whereas PAN remained inactive. Overall, these findings established that FBO-functionalized PAN nanofibers, particularly their Cu(II) complexes, are multifunctional materials with potent antioxidant, antidiabetic, antimicrobial, anti-biofilm, and photodynamic antimicrobial properties, offering promising potential for biomedical and therapeutic applications.
The reconstruction of skull base defects after tumor resection remains challenging due to the limitations of conventional materials, including poor mechanical properties, uncontrolled degradation, and insufficient osteoinduction. In this study, we developed a novel poly(lactic acid)/gelatin (PLA/Gel) fibrous membrane incorporating Fe3O4-modified hydroxyapatite whiskers (MHAw) to address these issues. The MHAw-containing membrane exhibited appropriate tensile strength, enhanced water absorption (>209.5%), and a degradation rate well-matched to bone regeneration (similar to 35% over 49 days). Cytotoxicity tests on SH-SY5Y neuroblastoma cells revealed significant inhibitory effects of MHAw and PGMH on cell viability, while live/dead staining confirmed high BMSC viability (>70%), meeting ISO 10993-5 safety requirements. Antibacterial assays further demonstrated substantial activity against clinically relevant pathogens. Collectively, this composite integrates suitable mechanical properties, controlled degradability, cytocompatibility, and antibacterial functionality, offering a promising scaffold for skull base repair.
Cerebral ischemia-reperfusion injury arises predominantly from excessive oxidative stress and sustained neuroinflammation. The selective cannabinoid receptor type 2 (CB2R) agonist AM1241 has shown potential to alleviate both pathological processes, yet its therapeutic efficacy is severely hampered by poor blood-brain barrier (BBB) permeability and inadequate intracerebral accumulation. To elevate the intracerebral therapeutic efficacy of AM1241, we constructed polydopamine-modified mesoporous silica nanoparticles (PMSNs) as nanocarriers to encapsulate AM1241, generating PMSNs@AM1241. Comprehensive physicochemical characterization confirmed that these nanoparticles exhibited uniform morphology, excellent dispersion, reliable storage stability, and pH-responsive drug release, enabling rapid AM1241 release in acidic environments. In vitro studies demonstrated that PMSNs@AM1241 exhibited high biocompatibility, could efficiently penetrate the blood-brain barrier, and were readily internalized by microglia. The nanomedicine effectively scavenged reactive oxygen species and suppressed neuronal apoptosis. It also inhibited the release of pro-inflammatory cytokines and reduced M1-like microglial marker expression while increasing M2-like marker expression via activation of CB2R and inhibition of the NF-kappa B signaling pathway, thereby exerting neuroprotective effects. In vivo, PMSNs@AM1241 significantly reduced brain edema, decreased infarct volume, attenuated histopathological damage, inhibited neuronal apoptosis, and markedly ameliorated neurological deficits in mice. Notably, the intrinsic antioxidant activity of PMSNs combined with the anti-inflammatory activity of AM1241 cooperatively modulated microglial inflammatory responses via the NF-kappa B signaling pathway, thereby attenuating oxidative stress and inflammatory cascades. Collectively, PMSNs@AM1241 represents an effective nanodelivery platform for cerebral ischemia-reperfusion injury, providing a novel strategy and experimental foundation.
Diabetic ulcers (DU), commonly caused by impaired circulation and bacterial infection, remain a leading source of morbidity and mortality in patients with diabetes mellitus worldwide. Clindamycin (CLD) is recommended for mild to moderate DU infections, targeting Staphylococcus aureus and Streptococcus spp.; however, current CLD formulations still present several limitations. Therefore, the development of alternative dosage forms is essential to overcome these challenges. To develop a new strategy in delivering Clindamycin precisely to the target of action and controlled with a Hydrogel Forming Microneedle (HFM) system integrated with a PEG reservoir. Clindamycin will be made in the HFM system using the crosslink method of 2 types of polymers then Clindamycin will be formulated into a PEG reservoir with several types of PEG combinations from different MWs to optimize CLD loading, then physical and chemical characterization, ex vivo permeation and antibiofilm activity testing will be carried out. The HFM was successfully developed with desirable mechanical strength and reliable insertion performance (penetrate up to 72% of needle height). The results of the ex vivo permeation test showed that this formulation successfully delivered CLD through the dermal route with an efficiency of up to 85% (equivalent to 21.3 +/- 1.57 mg/mL). The antibiofilm activity of all three HFM formulations was significantly different (p < 0.05) from that of the plain hydrogel. The development of Clindamycin in the form of HFM integrated with a PEG reservoir produces a Clindamycin preparation with good, safe and non-invasive characteristics.
