A dual-ligand fusion peptide improves the brain-neuron targeting of nanocarriers in Alzheimer's disease mice

Neurological disorders such as Alzheimer's disease, stroke, and brain cancers are difficult to treat with current drugs as their delivery efficacy to the brain is severely hampered by the presence of the blood-brain barrier (BBB). Drug delivery systems have been extensively explored in recent decades aiming to circumvent this barrier. In particular, polymeric nanoparticles have shown enormous potentials owing to their unique properties, such as high tunability, ease of synthesis, and control over drug release profile. However, careful analysis of their performance in effective drug transport across the BBB should be performed using clinically relevant testing models. In this review, polymeric nanoparticle systems for drug delivery to the central nervous system are discussed with an emphasis on the effects of particle size, shape, and surface modifications on BBB penetration. Moreover, the authors critically analyze the current in vitro and in vivo models used to evaluate BBB penetration efficacy, including the latest developments in the BBB-on-a-chip models. Finally, the challenges and future perspectives for the development of polymeric nanoparticles to combat neurological disorders are discussed.

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Section: Tunable Nanoparticle Properties For Enhanced Bbb Transfermentioning

confidence: 99%

Development of Polymeric Nanoparticles for Blood–Brain Barrier Transfer—Strategies and Challenges

et al. 2021

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“…Finally, Guo et al recently developed a PNP coated with both a BBB-penetrating ligand and a neuron-targeting ligand for carrying the neuroprotective peptide NAP. NAP has been shown to provide neuroprotective activity against NMDA receptors and Aβ-mediated excitotoxicity by interacting with glial and neuronal tubulin, thereby promoting microtubule assembly and the protection of the neuronal cytoskeleton [185]. As explained above, the clinical application of NAP is restricted due to its enzymatic degradation, ineffective neuron targeting and reduced half-life in the bloodstream [185].…”

Section: Polymeric-based Nanoparticles For Alzheimer's Diseasementioning

confidence: 99%

Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer’s disease: from current to future challenges

Cano

Turowski²,

Ettcheto

et al. 2021

J Nanobiotechnol

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Increasing life expectancy has led to an aging population, which has consequently increased the prevalence of dementia. Alzheimer's disease (AD), the most common form of dementia worldwide, is estimated to make up 50–80% of all cases. AD cases are expected to reach 131 million by 2050, and this increasing prevalence will critically burden economies and health systems in the next decades. There is currently no treatment that can stop or reverse disease progression. In addition, the late diagnosis of AD constitutes a major obstacle to effective disease management. Therefore, improved diagnostic tools and new treatments for AD are urgently needed. In this review, we investigate and describe both well-established and recently discovered AD biomarkers that could potentially be used to detect AD at early stages and allow the monitoring of disease progression. Proteins such as NfL, MMPs, p-tau217, YKL-40, SNAP-25, VCAM-1, and Ng / BACE are some of the most promising biomarkers because of their successful use as diagnostic tools. In addition, we explore the most recent molecular strategies for an AD therapeutic approach and nanomedicine-based technologies, used to both target drugs to the brain and serve as devices for tracking disease progression diagnostic biomarkers. State-of-the-art nanoparticles, such as polymeric, lipid, and metal-based, are being widely investigated for their potential to improve the effectiveness of both conventional drugs and novel compounds for treating AD. The most recent studies on these nanodevices are deeply explained and discussed in this review. Graphic Abstract

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“…In particular using small interfering RNAs (siR-NAs) some authors presented a "dual targeting" strategy based on nanoparticles (NP) built with a peptide component and a modified polyethylene glycol [110]. The peptide moiety was a BBB targeting peptide [111], more specifically it was the RI analogue of the all-L peptide TGNYKALHPHNG. The resulting NPs showed low toxicity and high transfection efficiency and were able to transfer siRNAs in the brain [112].…”

Section: Applications In Neurodegenerative Diseasesmentioning

confidence: 99%

Recent Applications of Retro-Inverso Peptides

Doti

Mardirossian

Sandomenico

et al. 2021

IJMS

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Natural and de novo designed peptides are gaining an ever-growing interest as drugs against several diseases. Their use is however limited by the intrinsic low bioavailability and poor stability. To overcome these issues retro-inverso analogues have been investigated for decades as more stable surrogates of peptides composed of natural amino acids. Retro-inverso peptides possess reversed sequences and chirality compared to the parent molecules maintaining at the same time an identical array of side chains and in some cases similar structure. The inverted chirality renders them less prone to degradation by endogenous proteases conferring enhanced half-lives and an increased potential as new drugs. However, given their general incapability to adopt the 3D structure of the parent peptides their application should be careful evaluated and investigated case by case. Here, we review the application of retro-inverso peptides in anticancer therapies, in immunology, in neurodegenerative diseases, and as antimicrobials, analyzing pros and cons of this interesting subclass of molecules.

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A dual-ligand fusion peptide improves the brain-neuron targeting of nanocarriers in Alzheimer's disease mice

Cited by 50 publications

References 64 publications

Development of Polymeric Nanoparticles for Blood–Brain Barrier Transfer—Strategies and Challenges

Development of Polymeric Nanoparticles for Blood–Brain Barrier Transfer—Strategies and Challenges

Nanomedicine-based technologies and novel biomarkers for the diagnosis and treatment of Alzheimer’s disease: from current to future challenges

Recent Applications of Retro-Inverso Peptides

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