A novel p-n junction photocatalyst of Bi4Ti3O12 nanofibers-BiOI nanosheets has been fabricated through a simple and economical technique of electrospinning combined with a successive ionic layer adsorption and reaction (SILAR) process. The products are characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectroscopy (XPS), UV-visible diffuse reflectance spectra (DRS), and photoluminescence (PL) spectroscopy. The as-formed Bi4Ti3O12 nanofibers are composed of inter-linked nanoparticles of 50-80 nm in size. The thickness of the as-grown BiOI nanosheets is about 10 nm and the size of the BiOI nanosheets increases with the SILAR cycles. In particular, many {001} facets of BiOI nanosheets are exposed, which is favorable to enhance the visible-light photocatalytic activity. The p-n junction photocatalyst exhibits enhanced visible-light-driven photocatalytic activity for decomposition of rhodamine B (RhB) and phenol. The enhanced photocatalytic activity can be attributed to the extended absorption in the visible light region resulting from the BiOI nanosheets and the effective separation of photogenerated carriers driven by the photo-induced potential difference generated at the Bi4Ti3O12-BiOI p-n junction interface.
As the most aggressive brain tumor, chemotherapy of malignant glioma remains to be extremely challenging in clinic. The blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) are physiological and pathological barriers preventing therapeutic drugs from reaching the glioma region. In addition, vasculogenic mimicry (VM) formed by invasive glioma cells instead of endothelial cells and angiogenesis are very common in glioma, leading to the poor prognosis and recurrence of glioma. An ideal drug delivery system for glioma chemotherapy needs to traverse the BBB and BBTB and then target VM, angiogenesis, and glioma cells. Herein we developed a liposome-based drug delivery system with the modification of proteolytically stable d-peptide ligands (CDX/A7R-LS). CDX is a d-peptide ligand of nicotine acetylcholine receptors (nAChRs) capable of circumventing the BBB, andA7R is a d-peptide ligand of vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) overexpressed on angiogenesis, VM, and glioma, presenting excellent glioma-homing property. CDX/A7R-LS could efficiently internalize into the brain capillary endothelial cells, glioma cells, tumor neovascular endothelial cells, and tumor spheroids and cross the in vitro BBB and BBTB models. Ex vivo imaging and in vivo immunofluorescence assays confirmed the superiority of CDX/A7R-LS in targeting intracranial glioma in comparison to plain liposomes or liposomes modified with an individual d-peptide ligand (either CDX orA7R). When loaded with doxorubicin, CDX/A7R-LS achieved the best antiglioma, antiangiogenesis, and anti-VM effects among all tested formulations. These results suggested that systemic glioma-targeted drug delivery enabled by all-d peptide ligands was promising for the antiglioma therapy.
Malignant glioma, the most frequent and aggressive central nervous system (CNS) tumor, severely threatens human health. One reason for its poor prognosis and short survival is the presence of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), which restrict the penetration of therapeutics into the brain at different stages of glioma. Herein, inspired by the peptide stapling technique, we designed a cyclic RGD ligand via an all-hydrocarbon staple (stapled RGD, sRGD) to facilitate BBB penetration while retaining the capacity of BBTB penetration and targeting ability to glioma cells. As expected, sRGD-modified micelles were able to penetrate the in vitro BBB model while retaining the glioma targeted capability. The results of the in vivo imaging studies further revealed that this nanocarrier could not only efficiently transverse the intact BBB of normal mice, but also could specifically target glioma cells of intracranial glioma-bearing nude mice. Furthermore, Paclitaxel-loaded sRGD-modified micelles exhibited improved antiglioma efficacy in vitro and significantly prolonged survival time of glioma-bearing nude mice. Overall, this sRGD peptide showed potency for glioma-targeted drug delivery by overcoming multiple barriers.
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