Glioma, the most prevalent primary intracranial tumor, presents significant clinical treatment challenges due to its high invasiveness and therapeutic resistance. Therefore, the development of a targeted therapeutic agent that is both highly effective and low in toxicity is crucial. In this research, we aimed to design a bionic mesoporous selenium nanoparticle (ACMLMSeP) functionalized with paclitaxel and Ang-2 for nasal administration as a targeted treatment approach for glioma. Nasal administration facilitates direct delivery of drugs to the brain through the olfactory nerve, thereby circumventing the protective mechanisms of the blood-brain barrier. Mesoporous selenium (MSe) significantly enhances the loading capacity for insoluble drugs while improving their water solubility. The functionalization of MSe enables slow drug release and facilitates targeted drug accumulation. Moreover, accumulated nano-selenium promotes reactive oxygen species (ROS) production, induces autophagy, and synergizes with drugs to accelerate apoptosis in tumor cells. Analysis using Transmission Electron Microscopy (TEM) images and Dynamic Light Scattering (DLS) indicated that ACMLMSe has an average particle size of roughly 135 nm. Results from in vitro release assessments indicated that the ACMLMSeP sustained the release of the drug, reaching a total release rate of 74.96 ± 2.34 % within 24 h. Cellular uptake studies and in vivo imaging showed the strong targeting capabilities of the ACMLMSeP nanoparticles. Furthermore, the results obtained from the MTT assays, flow cytometry analysis, immunofluorescence staining, and in vivo antitumor evaluations collectively revealed that ACMLMSeP effectively inhibited proliferation while promoting apoptosis in C6 cells. In summary, these experimental findings clearly suggest that ACMLMSeP may serve as a promising biomimetic nanosystem for the targeted treatment of brain glioma.
Meng Zhang,Yumei Wang,Jiayi Wang,Jiayi Zuo,Feng Jiang,Feng Cao
Neovascular ocular diseases are a leading cause of irreversible vision loss. Although intravitreal anti-VEGF therapy is the standard treatment, its invasive delivery and limited efficacy in some patients emphasize the need for non-invasive strategies targeting multiple angiogenic pathways. In this study, we developed a novel hybrid nanoplatform for the non-invasive co-delivery of axitinib (Axi) and telmisartan (Tel) to synergistically inhibit both VEGF and Ang-2 signaling pathways. Poorly soluble drugs were incorporated into layered double hydroxides (LDHs) via a micelle-assisted intercalation strategy and subsequently modified with hyaluronic acid (HA) conjugated to Gly-Val-Sar (GVS), a novel PepT1-targeted tripeptide. The Zn-containing LDH provided controlled drug release, and exhibited anti-inflammatory properties. HA modification prolonged ocular retention, and GVS enhanced transmembrane transport. The resulting Axi/Tel-D@LDH-HA-GVS nanocomposites demonstrated favorable physicochemical properties, efficient uptake by human conjunctival and retinal pigment epithelial cells, and potent inhibition of hypoxia-induced angiogenesis in vitro. In vivo, the formulations exhibited prolonged ocular retention, effective posterior tissue distribution, and good biosafety. In a diabetic retinopathy model, Axi/Tel-D@LDH-HA-GVS nanocomposites restored retinal structure and markedly reduced the expression of VEGF, Ang-2, TNF-α, and IL-6. Collectively, this study provides a promising non-invasive and synergistic strategy for targeted treatment of ocular neovascular diseases.
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