Neuronanomedicine for Alzheimer's and Parkinson's disease: Current progress and a guide to improve clinical translation.

Neuronanomedicine is an emerging multidisciplinary field that aims to create innovative nanotechnologies to treat major neurodegenerative disorders, such as Alzheimer's (AD) and Parkinson's disease (PD). A key component of neuronanomedicine are nanoparticles, which can improve drug properties and demonstrate enhanced safety and delivery across the blood-brain barrier, a major improvement on existing therapeutic approaches. In this review, we critically analyze the latest nanoparticle-based strategies to modify underlying disease pathology to slow or halt AD/PD progression. We find that a major roadblock for neuronanomedicine translation to date is a poor understanding of how nanoparticles interact with biological systems (i.e., bio-nano interactions), which is partly due to inconsistent reporting in published works. Accordingly, this review makes a set of specific recommendations to help guide researchers to harness the unique properties of nanoparticles and thus realise breakthrough treatments for AD/PD.

Characterizing the Dynamic Disassembly/Reassembly Mechanisms of Encapsulin Protein Nanocages.

Encapsulins, self-assembling icosahedral protein nanocages derived from prokaryotes, represent a versatile set of tools for nanobiotechnology. However, a comprehensive understanding of the mechanisms underlying encapsulin self-assembly, disassembly, and reassembly is lacking. Here, we characterize the disassembly/reassembly properties of three encapsulin nanocages that possess different structural architectures: T = 1 (24 nm), T = 3 (32 nm), and T = 4 (42 nm). Using spectroscopic techniques and electron microscopy, encapsulin architectures were found to exhibit varying sensitivities to the denaturant guanidine hydrochloride (GuHCl), extreme pH, and elevated temperature. While all three encapsulins showed the capacity to reassemble following GuHCl-induced disassembly (within 75 min), only the smallest T = 1 nanocage reassembled after disassembly in basic pH (within 15 min). Furthermore, atomic force microscopy revealed that all encapsulins showed a significant loss of structural integrity after undergoing sequential disassembly/reassembly steps. These findings provide insights into encapsulins' disassembly/reassembly dynamics, thus informing their future design, modification, and application.