Dong Han,Baolin Zhang,Chuangang Chong,Cuiping Rong,Jie Tan,Rusen Yang
Effective attachment of magnetic nanoparticles to neuronal membranes has far-reaching significance in activating ion channels and treating neurodegenerative diseases. Superparamagnetic iron oxide nanoparticles (SPIONs) synthesized by the polyol pyrolysis method have the advantages of rich surface functional groups, excellent magnetic properties, controllable particle size and water dispersibility. We propose that perfusion of biotin into the targeted brain area should be initially performed because it tends to be adsorbed by cell membranes, followed by injection of streptavidin (SA)-modified SPIONs into the same area of the brain. By means of the strong binding force between SA and biotin, the SPIONs may subsequently adhere to the cell surfaces in the brain area. In this work, fluorescein isothiocyanate-streptavidin (FITC-SA) was modified on the surface of polyethylene imine (PEI)-SPIONs by the EDC–NHS method and stereotaxically injected into the biotin-supplemented substantia nigra of mice. The combination of fluorescence detection with transmission electron microscopy (TEM) confirmed that FITC-SA/PEI-SPIONs adhered to neuronal membranes in the substantia nigra of mice 24 h after injection. The results show that our strategy can promote the attachment of SPIONs to neuronal membranes.
Transcatheter arterial chemoembolization (TACE) is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Blood-vessel-embolic agents play key role on TACE. In the present work, we reported a Bletilla striata polysaccharide/poly (N-isopropylacrylamide) (BSP/PNIPAM) thermosensitive microemulsion gel loaded with magnetic icaritin (ICT) microemulsion (IS-MEs) as embolic agent (ISBP) for the first time. IS-MEs co-loaded with ICT and superparamagnetic iron oxide nanoparticles (SPIONs) were prepared by water titration method. The particle size of IS-MEs was 27.97 ± 0.25 nm, encapsulation efficiency was 97.18%, and presented a regular sphere under TEM. BSP/PNIPAM was prepared by free radical polymerization, which has good biocompatibility, excellent procoagulant function and dense microstructure. The lower critical solution temperature (LCST) of ISBP was 30 °C, which had excellent in vitro injection performance. The microscopic morphology of ISBP was loose and porous, the long-acting sustained-release time could reach 144 h, and the maximum ICT release was (48.6 ± 8.5) %. IPSBs with SPIONs exhibit desirable imaging properties and macrophage M1 polarization function. During the rabbit renal artery embolization, ISBP showed excellent distal vascular embolization performance and there was no obstruction or adhesion of the catheter. These results suggest that a novel in situ multifunctional traditional Chinese medicine thermosensitive microemulsion gel embolic agent has been developed with a potential application as a liquid embolic solution for TACE.
Photothermal therapy (PTT) is a promising strategy for cancer treatment, but its clinical application relies heavily on accurate tumor positioning and effective combination. Nanotheranostics has shown superior application in precise tumor positioning and treatment, bringing potential opportunities for developing novel PTT-based therapies. Here, a nanotheranostic agent is proposed to enhance magnetic resonance imaging (MRI)/ near-infrared fluorescence imaging (NIRFI) imaging-guided photo-induced triple-therapy for cancer. Thermosensitive liposomes co-loaded with SPIONs/IR780 and Abemaciclib (SIA-TSLs), peptide ACKFRGD, and click group 2-cyano-6-amino-benzothiazole (CABT) are co-modified on the surface of SIA-TSLs to form SIA- α TSLs. ACKFRGD can be hydrolyzed to expose the 1, 2-thiolamino groups in the presence of cathepsin B in tumors, which click cycloaddition with the cyano group on CABT, resulting in the formation of SIA- α TSLs aggregates. The aggregation of SIA- α TSLs in tumors enhances the MRI/NIRFI imaging capability and enables precise PTT. Photo-induced triple-therapy enhances precision cancer therapy. First, PTT ablates specific tumors and induces ICD via localized photothermal. Second, local tumor heating promotes the rupture of SIA- α TSLs, which release Abemaciclib to block the tumor cell cycle and inhibit Tregs proliferation. Third, injecting GM-CSF into tumor tissue leads to recruitment of dendritic cells and initiation of antitumor immunity. Collectively, these results present a promising nanotheranostic strategy for future cancer therapy.