Engineering Macrophage Exosome Disguised Biodegradable Nanoplatform for Enhanced Sonodynamic Therapy of Glioblastoma

Abstract

Sonodynamic therapy (SDT) exhibits high tissue penetration and negligible radiation damage to normal tissues, and thus emerges as a promising cancer therapeutic modality for glioblastoma (GBM). However, the blood−brain barrier (BBB) and hypoxic microenvironment greatly limit the SDT efficiency. In this work, a biodegradable nanoplatform (termed as CSI) is fabricated by encapsulating catalase (CAT) into silica nanoparticles (CAT@SiO2) for tumor hypoxia relief, and then loaded with the sonosensitizer indocyanine green (ICG). Inspired by the ability of macrophages to cross the BBB, CSI is further coated with AS1411 aptamer‐modified macrophage exosomes to form CSI@Ex‐A, which possesses efficient BBB penetration and good cancer‐cell‐targeting capability. After tumor cell endocytosis, highly expressed glutathione (GSH) triggeres biodegradation of the nanoplatform and the released CAT catalyzes hydrogen peroxide (H2O2) to produce O2 to relieve tumor hypoxia. The GSH depletion and O2 self‐supplying effectively enhances the SDT efficiency both in vitro and in vivo. In addition, the resulting CSI@Ex‐A exhibits good biocompatibility and long circulation time. These findings demonstrate that CSI@Ex‐A may serve as a competent nanoplatform for GBM therapy, with potential for clinical translation.

Engineered tumor cell-derived vaccines against cancer: The art of combating poison with poison

“…However, large-scale application of this method is difficult. Therefore, an ultrasonic method was proposed in which membrane-encapsulated nanoparticles were produced by sonicating vesicles or cell membranes with nanoparticles [ 68 ]. Despite the simplicity of the approach, the time and power of the ultrasound should be optimized to obtain maximum fusion efficiency with minimal damage to the membrane-coated nanoparticles.…”

Targeting tumor-associated macrophages for the immunotherapy of glioblastoma: Navigating the clinical and translational landscape

“…Novel noninvasive physical approaches with few toxic adverse effects have been used to eliminate GBM cells in translational studies, including photothermal therapy(PTT) ( 120 , 124 ), photodynamic therapy(PDT) ( 140 ), and sonodynamic therapy(SDT) ( 116 ). Phototherapy consisting of PTT and PDT, relies on phototherapeutic agents and light irradiation to kill tumor cells in the dark ( 143 ).…”

“…In another study, the performance of engineered macrophage-derived sEVs containing glutathione (GSH)-responsive silica nanoparticles (NPs) was evaluated in GBM mouse model. The silica NPs were coated with indocyanine green (ICG) and encapsulated with catalase (CAT), which led to oxygen generation and reversed the hypoxic TME of GBM ( 116 ). On a mechanistic level, ICG plays the role of a sonosensitizer in sonodynamic therapy (SDT) following ultrasound irradiation to increase the level of ROS, thus causing GBM cell necrosis.…”

Functionalized Macrophage Exosomes with Panobinostat and PPM1D‐siRNA for Diffuse Intrinsic Pontine Gliomas Therapy

“…[ 42 ] Engineering macrophage exosome encapsulating silica nanoparticles possesses efficient BBB penetration and good targeting capability for glioblastoma. [ 45 ] Thus, macrophages exosomes have great application potential in the treatment of brainstem gliomas.…”