A Core–Shell Nanoplatform for Synergistic Enhanced Sonodynamic Therapy of Hypoxic Tumor via Cascaded Strategy

Abstract

Sonodynamic therapy (SDT) always causes tumor hypoxia aggravation which can induce malignant cell proliferation and drug resistance. To overcome these disadvantages, a cascaded drug delivery system (Lipo/HMME/ACF@MnO2‐AS1411) is constructed for synergistic enhanced sonodynamic therapy. First, hematoporphyrin monomethyl ether (HMME) and acriflavine (ACF) are encapsulated in the lipid layers and the inner aqueous cores of the liposomes, respectively. Then the ultrathin manganese dioxide (MnO2) nanosheets are coated on the surface of the liposomes by using KMnO4 and polyethylene glycol through “one step reduction and modification” method. Furthermore, the nanoparticles are decorated with tumor‐targeting AS1411 aptamer through the phosphate groups on the DNA strand which can bind to Mn sites to obtain Lipo/HMME/ACF@MnO2‐AS1411 delivery system. Herein, HMME can act as a sonosensitizer, and ACF is used to prevent the formation of HIF‐1α/HIF‐1β dimerization to overcome the negative effects after SDT. The Lipo/HMME/ACF@MnO2‐AS1411 delivery system has multiple functions, including codelivery of HMME and ACF, pH/glutathione/ultrasound triple responses, synergistic cascaded enhancement of SDT, precise tumor‐targeting, and magnetic resonance imaging. The in vitro and in vivo results suggest that the Lipo/HMME/ACF@MnO2‐AS1411 delivery system is a promising core–shell nanoplatform for synergistic enhancement of sonodynamic therapy, which can provide a new approach in the related research fields.

Ultrasound‐Activated Sensitizers and Applications

“…Copyright 2016, American Chemical Society. (D) Reproduced with permission . Copyright 2018, Wiley‐VCH.…”

“…To solve this problem, Wang et al. developed a cascading pH/GSH/US‐responsive drug delivery system (Lipo/HMME/ACF@MnO 2 ‐AS1411; Figure D) . The system released the drug in a controlled manner in response to the specific stimulation as well as aptamer (APT) enabled targeted drug delivery and accumulation at the tumor site to enhance the therapeutic efficacy.…”

“…C) The elemental mapping of MCC. D,E) TEM images of HMME/MCC‐HA irradiated by US for 30 s and 60 s. (A–E) Reproduced with permission . Copyright 2017, Wiley‐VCH.…”

Ultraschallaktivierte Sensibilisatoren

“…Um dieses Problem zu lösen, haben Wang et al. ein kaskadierendes pH/GSH/US‐responsives Wirkstoffabgabesystem entwickelt (Lipo/HMME/ACF@MnO 2 ‐AS1411) (Abbildung D) . Das System setzte den Wirkstoff in kontrollierter Weise als Antwort auf die spezifische Stimulation frei, und ein Aptamer (APT) ermöglichte die gezielte Wirkstoffabgabe und Akkumulation an der Tumorstelle, um die therapeutische Wirksamkeit zu verbessern.…”

“…C) Elementkartierung von MCC. D,E) TEM‐Aufnahmen von HMME/MCC‐HA bestrahlt mit US für 30 s und 60 s. (A–E) Abdruck mit Genehmigung . Copyright 2017, Wiley‐VCH.…”