An Antisense Oligonucleotide-Loaded Blood–Brain Barrier Penetrable Nanoparticle Mediating Recruitment of Endogenous Neural Stem Cells for the Treatment of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a neurodegenerative disease characterized by the death of dopaminergic (DA) neurons and currently cannot be cured. One selected antisense oligonucleotide (ASO) is reported to be effective for the treatment of PD. However, ASO is usually intrathecally administered by lumbar puncture into the cerebral spinal fluid, through which the risks of highly invasive neurosurgery are the major concerns. In this study, ZAAM, an ASO-loaded, aptamer Apt 19S-conjugated, neural stem cell membrane (NSCM)-coated nanoparticle (NP), was developed for the targeted treatment of PD. NSCM facilitated the blood–brain barrier (BBB) penetration of NPs, and both NSCM and Apt 19S promoted the recruitment of the neural stem cells (NSCs) toward the PD site for DA neuron regeneration. The behavioral tests demonstrated that ZAAM highly improved the efficacy of ASO on PD by the targeted delivery of ASO and the recruitment of NSCs. This work is a heuristic report of (1) nonchemoattractant induced endogenous NSC recruitment, (2) NSCM-coated nanoparticles for the treatment of neurodegenerative diseases, and (3) systemic delivery of ASO for the treatment of PD. These findings provide insights into the development of biomimetic BBB penetrable drug carriers for precise diagnosis and therapy of central nervous system diseases.

A metal–organic cage-derived cascade antioxidant nanozyme to mitigate renal ischemia-reperfusion injury

“…To investigate the biocompatibility of MOC-O in major organs including the heart, liver, lungs and kidneys in mice, tissue samples were collected after two days of treatment and subjected to histological analysis using hematoxylin and eosin (H&E) staining. 2,36 As shown in Fig. 4A, all organs from the three groups exhibited uniform organization with no apparent signs of damage.…”

“…Nonetheless, these bean-shaped organs are quite susceptible to various stressful conditions, particularly I/R injury, due to their high oxygen demand. 1,2 I/R injury is a common cause of kidney damage, often resulting from medical procedures such as kidney transplantation. This injury occurs when the blood supply to the kidneys is temporarily blocked, resulting in a lack of oxygen and nutrients.…”

Simultaneous antioxidant and neuroprotective effects of two-dimensional (2D) MXene-loaded isoquercetin for ischemic stroke treatment

“…Ti 2 C@BSA-ISO has acceptable therapeutic results compared to previous studies. 24,43,60 The long-held belief that titanium is inert and safe for human use can be seen as one of the main reasons for using titanium as an implant. 61 Compared to other elements (Mn, Cu), Ti 2 C@BSA-ISO has a safe composition and has a broader scope for disease treatment.…”

Advancing Epidemiology and Genetic Approaches for the Treatment of Spinal and Bulbar Muscular Atrophy (SBMA): Focus on Prevalence in the Indigenous Population of Western Canada

“…Of note, both groups were limited by the inability of their gapmers to cross the blood-brain barrier, requiring mutually exclusive treatment of either the CNS or peripheral muscles based on injection type. Interestingly, recent studies have identified numerous nanocarriers and apoptotic bodies which can successfully facilitate oligonucleotide penetration of the blood-brain barrier [65][66][67].…”