Anti-MicroRNA-21 Oligonucleotide Loaded Spermine-Modified Acetalated Dextran Nanoparticles for B1 Receptor-Targeted Gene Therapy and Antiangiogenesis Therapy

The use of nanoparticles (NPs) to deliver small inhibiting microRNAs (miRNAs) has shown great promise for treating cancer. However, constructing a miRNA delivery system that targets brain cancers, such as glioblastoma multiforme (GBM), remains technically challenging due to the existence of the blood‐tumor barrier (BTB). In this work, a novel targeted antisense miRNA‐21 oligonucleotide (ATMO‐21) delivery system is developed for GBM treatment. Bradykinin ligand agonist‐decorated spermine‐modified acetalated dextran NPs (SpAcDex NPs) could temporarily open the BTB by activating G‐protein‐coupled receptors that are expressed in tumor blood vessels and tumor cells, which increase transportation to and accumulation in tumor sites. ATMO‐21 achieves high loading in the SpAcDex NPs (over 90%) and undergoes gradual controlled release with the degradation of the NPs in acidic lysosomal compartments. This allows for cell apoptosis and inhibition of the expression of vascular endothelial growth factor by downregulating hypoxia‐inducible factor (HIF‐1α) protein. An in vivo orthotopic U87MG glioma model confirms that the released ATMO‐21 shows significant therapeutic efficacy in inhibiting tumor growth and angiogenesis, demonstrating that agonist‐modified SpAcDex NPs represent a promising strategy for GBM treatment combining targeted gene therapy and antiangiogenic therapy

Magnetofluorescent Carbon Quantum Dot Decorated Multiwalled Carbon Nanotubes for Dual-Modal Targeted Imaging in Chemo-Photothermal Synergistic Therapy

Magnetofluorescent nanoparticles with diagnostic and therapeutic functions show great promise in nanomedicine. Here, we report the magnetofluorescent carbon nanotubes (CNTs)/doxorubicin (DOX) nanocomposites and their functions act in synergetic chemo-photothermal synergistic therapy (Chemo/PTT) in cancer excision. Magnetofluorescent CNTs conjugated with a folic acid (FA-GdN@CQDs-MWCNTs) were targets for dual-modal fluorescence (FL)/magnetic resonance (MR) imaging. Experiments in vitro and in vivo identified FA-GdN@CQDs-MWCNTs with low toxicity, and good biocompatibility. Moreover, FA-GdN@CQDs-MWCNTs whose release can be fostered by pH and NIR light dual-stimuli had been proved to be available for loading DOX. Following nuclear translocations, FA-GdN@CQDs-MWCNTs were engineered to deliver DOX that targeted the nuclei. In vivo experiment indicates that the Chemo/PTT, as compared with the respective single treatment, can significantly control tumor growth. In addition, Chemo/PTT was not shown to render any appreciable toxicity. These findings suggest that the FA-GdN@CQDs-MWCNTs/DOX could function as a multifunctional platform for simultaneous FL/MR imaging, PTT therapy, and drug delivery