Engineering nanomedicines for neuroprotection and neuroregeneration in spinal cord injury

Traumatic spinal cord injury (SCI) is a severe condition of the central nervous system that can lead to axonal degeneration and neuronal cell death, resulting in the loss of sensory and motor function [1], [2]. Therapeutic agents (e.g., chemical drugs, nucleic acids, proteins) have been attempted to improve SCI therapy. Unfortunately, various delivery barriers, including rapid clearance, limited ability to cross the blood-spinal cord barrier (BSCB) or blood-brain barrier (BBB), and low spinal cord-specific accumulation, compromised their efficacy on SCI therapy [3], [4], [5].

Nanomedicine has emerged as a promising interdisciplinary approach for improving the therapeutic effects of SCI, and nanomaterials have been extensively investigated in SCI therapy, ranging from micelles, liposomes, nanofibers, nanovesicles and so forth, offering high potency and safety (Fig. 1) [5], [6], [7], [8], [9], [10], [11], [12], [13], [14]. The following are some ways nanomaterials are being used to address the limitations of traditional medication: (1) improving bioavailability [15]; (2) prolonging blood circulation [16]; (3) enhancing BBB/BSCB permeability [4], [17]; (4) ensuring targeted delivery [18]; (5) achieving controlled release in the lesioned spinal cord [19]. Furthermore, certain nanomaterials possess inherent biofunctions beneficial for SCI management. For instance, exosomes, which are nanoscale components of the cellular secretome, play a crucial role in cellular communication and the regulation of SCI biology. They exhibit low immunogenicity and high BSCB permeability, making them suitable for tissue repair and functional recovery post-SCI, either alone or in combination with medications [20], [21].

Here, we review the multiple nanomedicine therapies for SCI. Firstly, we outline the pathological progression of SCI that is mainly conceptualized into two categories: primary mechanical injury and secondary injury. Next, available strategies focus predominantly on neuroprotection and neuroregeneration, aimed at preserving neurons and enhancing neuronal regeneration separately [5], [22], [23]. We elaborate on neuroprotective nanomedicine, which restores environmental homeostasis and repairs damaged structures, and neuroregenerative nanomedicine, which optimizes extrinsic and intrinsic regenerative capacity. Finally, we outlook the obstacles and efforts to the clinical translation of nanomedicine therapies. Through this review, we aim to offer new insights and inspire researchers to develop more effective and precise interventions for SCI.