Glutathione-Sensitive Nanoglue Platform with Effective Nucleic Acids Gluing onto Liposomes for Photo-Gene Therapy

Abstract

Liposomal spherical nucleic acids possess a high density of nucleic acids, e.g., DNA, on a liposomal core. There are two approaches to conjugate DNA onto the zwitterionic liposomes, i.e., covalent and noncovalent conjugation, otherwise using cationic liposomes. However, complex and expensive DNA chemical modification methods need to seek a novel and easy-operating approach to decorating DNA onto liposomes. Inspired by the nanoparticle solution as nanoglues for gels and biological tissues, we use MnO 2 nanosheets to "glue" DNA onto liposomes without DNA modification. In tumor cells with a high glutathione concentration, MnO 2 -based nanoglues are degraded, generating water-soluble Mn 2+ ions, further "unglue" DNA (i.e., DNAzyme), and liposomes. Using the intelligent liposomal nanoglue (DNAzyme/MnO 2 /Lip) combining glutathione-sensitive MnO 2 nanosheets, gene silencing agent DNAzyme, and photosensitizer Chlorin e6 (Ce6) in liposomes, effective photo-gene therapy was demonstrated.

Therapeutic DNAzymes: From Structure Design to Clinical Applications

“…Simultaneously, integration of nanomaterials to enhance the catalytic efficiency of both photosensitizers and DNAzymes further inhibits cancer progression. [172] Photothermal therapy (PTT) is hindered by HSP upregulation under heat stress. To date, HSP-targeted DNAzymes have been widely designed to boost photothermal therapy.…”

“…Adapted with permission. [ 172 ] Copyright 2022, American Chemical Society. E) Illustration describing the DNAzyme system with enhanced lysosome escaped effect, to achieve gene–PDT combination treatment.…”

“…D) Fabrication of liposomal nanoglue platform for DNAzymes and photosensitizer Ce6 coloading. Adapted with permission [172]. Copyright 2022, American Chemical Society.…”

New Hope for Treating Intervertebral Disc Degeneration: Microsphere-Based Delivery System

“…In recent years, research on nonviral gene delivery has become popular. From the nanoscale (e.g., liposomes ( Wang et al, 2021 ; Yu et al, 2022 ), complex micelles ( Yoshinaga et al, 2021 ; Yoshinaga et al, 2022 ), and exosomes ( Cui et al, 2022 ; Xu et al, 2022 )) to the micron scale (such as microspheres ( McMillan et al, 2018 ; Hinkelmann et al, 2022 )) or combined forms of nanoparticles and microspheres ( Feng et al, 2017 ; Feng et al, 2020 ; Chang et al, 2022 ), more options for nonviral vectors have been provided. Importantly, genetic factors contribute to the worsening of IVDD, and gene therapy approaches are expected to improve the poor genetic cascade regulation of IVD.…”

Multifunctional Hollow MnO2@Porphyrin@Bromelain Nanoplatform for Enhanced Photodynamic Therapy

“…A lot of efforts have been made by exploring different materials for oxygen delivering, such as perfluorocarbon, calcium peroxide, and MnO 2 . [15][16][17] Among them, manganese dioxide (MnO 2 ) exhibits the activity of catalase, which can catalyze hydrogen peroxide (H 2 O 2 ) to generate oxygen (O 2 ). Thus, the MnO 2based PDT system can effectively alleviate the hypoxic state of the TME and enhance the effect of PDT.…”