Blood–Brain Barrier‐Penetrating and Lesion‐Targeting Nanoplatforms Inspired by the Pathophysiological Features for Synergistic Ischemic Stroke Therapy

Brain disorders represent a significant challenge in medical science due to the formidable blood‐brain barrier (BBB), which severely limits the penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into the innovative realm of biomimetic nanodelivery systems, including stem cell‐derived nanoghosts, tumor cell membrane‐coated nanoparticles, and erythrocyte membrane‐based carriers, highlighting their potential to circumvent the BBB's restrictions. By mimicking native cell properties, these nanocarriers emerge as a promising solution for enhancing drug delivery to the brain, offering a strategic advantage in overcoming the barrier's selective permeability. We evaluate the unique benefits of leveraging cell membranes from various sources and examine advanced technologies for fabricating cell membrane‐encapsulated nanoparticles capable of masquerading as endogenous cells. This enables the targeted delivery of a broad spectrum of therapeutic agents, ranging from small molecule drugs to proteins, thereby providing an innovative approach to neurocare. Furthermore, the review contrasts the capabilities and limitations of these biomimetic nanocarriers with traditional delivery methods, underlining their potential to enable targeted, sustained, and minimally invasive treatment modalities. We conclude with a perspective on the clinical translation of these biomimetic systems, underscoring their transformative impact on the therapeutic landscape for intractable brain diseases.This article is protected by copyright. All rights reserved

Revolutionizing Neurocare: Biomimetic Nanodelivery Via Cell Membranes

Liao,

Gong,

et al. 2024

A Full‐Process, Fine‐Grained, and Quantitative Rehabilitation Assessment Platform Enabled by On‐Skin Sensors and Multi‐Task Gait Transformer Model

Wang,

He,

et al. 2024

Rehabilitation of patients with lower limb movement disorders is a gradual process, which requires full‐process assessments to guide the implementation of rehabilitation plans. However, the current methods can only complete the assessment in one stage and lack objective and quantitative assessment strategies. Here, a full‐process, fine‐grained, and quantitative rehabilitation assessments platform (RAP) supported by on‐skin sensors and a multi‐task gait transformer (MG‐former) model for patients with lower limb movement disorders is developed. The signal quality and sensitivity of on‐skin sensor is improved by the synthesis of high‐performance triboelectric material and structure design. The MG‐former model can simultaneously perform multiple tasks including binary classification, multiclassification, and regression, corresponding to assessment of fall risk, walking ability, and rehabilitation progress, covering the whole rehabilitation cycle. The RAP can assess the walking ability of 23 hemiplegic patients, which has highly consistent results with the scores by the experienced physician. Furthermore, the MG‐former model outputs fine‐grained assessment results when performing regression task to track slight progress of patients that cannot be captured by conventional scales, facilitating adjustment of rehabilitation plans. This work provides an objective and quantitative platform, which is instructive for physicians and patients to implement effective strategy throughout the whole rehabilitation process.

Inhibiting Mitochondrial Damage for Efficient Treatment of Cerebral Ischemia‐Reperfusion Injury Through Sequential Targeting Nanomedicine of Neuronal Mitochondria in Affected Brain Tissue

Wang,

Shi,

Xiong

et al. 2024

Oxidative stress, predominantly from neuronal mitochondrial damage and the resultant cytokine storm, is central to cerebral ischemia‐reperfusion injury (CIRI). However, delivering drugs to neuronal mitochondria remains challenging due to the blood‐brain barrier (BBB), which impedes drug entry into affected brain tissues. This study introduces an innovative tannic acid (TA) and melanin‐modified heteropolyacid nanomedicine (MHT), which highly specifically eliminates the neuronal mitochondrial reactive oxygen radicals burst to efficiently reduce neuronal mitochondrial damage through a strategically designed sequential targeting strategy from affected brain tissue to neuronal mitochondria. TA endows MHT with sequential targeting ability by binding to matrix proteins exposed to the damaged BBB and mitochondrial outer membrane proteins of neurons, while melanin significantly enhances the antioxidant capacity of MHT. Consequently, MHT effectively inhibits neuronal apoptosis by protecting mitochondria and reversing the inflammatory immune environment through the deactivation of the cyclic GMP‐AMP synthase–stimulator of interferon genes (cGAS‐STING) pathway. MHT demonstrated a strong therapeutic effect on CIRI, with an ultralow dose (2 mg kg−1) proving effective in reversing the condition. This work not only introduces a new avenue to significantly reduce CIRI through sequential targeting therapy but also offers a new paradigm for treating other ischemia‐reperfusion injury diseases.