Tailored Apoptotic Vesicle Delivery Platform for Inflammatory Regulation and Tissue Repair to Ameliorate Ischemic Stroke

Abstract

Apoptotic vesicles (ApoVs) hold great promise for inflammatory regulation and tissue repair. However, little effort has been dedicated to developing ApoV-based drug delivery platforms, while the insufficient targeting capability of ApoVs also limits their clinical applications. This work presents a platform architecture that integrates apoptosis induction, drug loading, and functionalized proteome regulation, followed by targeting modification, enabling the creation of an apoptotic vesicle delivery system to treat ischemic stroke. Briefly, α-mangostin (α-M) was utilized to induce mesenchymal stem cell (MSC) apoptosis while being loaded onto MSC-derived ApoVs as an anti-oxidant and anti-inflammatory agent for cerebral ischemia/​reperfusion injury. Matrix metalloproteinase activatable cell-penetrating peptide (MAP), a microenvironment-responsive targeting peptide, was modified on the surface of ApoVs to obtain the MAP-functionalized α-M-loaded ApoVs. Such engineered ApoVs targeted the injured ischemic brain after systemic injection and achieved an enhanced neuroprotective activity due to the synergistic effect of ApoVs and α-M. The internal protein payloads of ApoVs, upon α-M activation, were found engaged in regulating immunological response, angiogenesis, and cell proliferation, all of which contributed to the therapeutic effects of ApoVs. The findings provide a universal framework for creating ApoV-based therapeutic drug delivery systems for the amelioration of inflammatory diseases and demonstrate the potential of MSC-derived ApoVs to treat neural injury.

Bioactive Ceria Nanoenzymes Target Mitochondria in Reperfusion Injury to Treat Ischemic Stroke

“…Brain edema is a common pathological feature of IS; , thus, we used the dry–wet weight method to evaluate the extent of edema in the infarcted hemispheres of the mice (Figure H). Compared with the sham surgery group, the brain water content in the infarcted hemispheres of MCAO rats increased significantly from 76.83% to 84.11%.…”

“…Excess ROS are well-known contributors to neuronal mitochondrial dysfunction, which is an early event in the pathogenesis of ischemic stroke . CeNZs possess dynamic and reproducible ROS scavenging abilities due to their reversible conversion between the two valence states (Figure A).…”

Biologically Self-Assembled Tumor Cell-Derived Cancer Nanovaccines as an All-in-One Platform for Cancer Immunotherapy

“…Interestingly, the tumor metastasis-associated proteins declined in αM-Exos compared with those in B-Exos and Exos (Figure H, Table S1), which are possibly caused by the antitumor effects of αM. αM, a xanthone compound isolated from mangosteen husk, has been reported for the treatment of tumor metastasis in various cancer types. − Therefore, in addition to enhancing the immunogenicity of αM-Exos, αM may inhibit the invasion of tumor cells, thereby reducing the pro-metastatic risk of TEXs in αM-Exos and improving the safety of αM-Exos.…”

Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions

“…For targeted delivery to the ischemic region of the brain, the apoptotic vesicles were surface-modified with matrix metalloproteinase (MMP) activatable cell-penetrating peptide. The engineered apoptotic vesicles demonstrated angiogenesis, cell proliferation, and improved functional recovery in vivo [ 310 ]. It is evident that EVs hold great promise for early diagnosis and treatment of ischemic stroke.…”