Year-end Sale % OFF 
Abstract
BackgroundAlthough many therapeutic strategies for Alzheimer’s disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau.ResultsCurcumin (CUR) is loaded onto red blood cell (RBC) membrane-coated PLGA particles bearing T807 molecules attached to the RBC membrane surface (T807/RPCNP). With the advantage of the suitable physicochemical properties of the PLGA nanoparticles and the unique biological functions of the RBC membrane, the RPCNP are stabilized and promote sustained CUR release, which provided improved biocompatibility and resulted in long-term presence in the circulation. Under the synergistic effects of T807, T807/RPCNP can not only effectively penetrate the blood–brain barrier (BBB), but they also possess high binding affinity to hyperphosphorylated tau in nerve cells where they inhibit multiple key pathways in tau-associated AD pathogenesis. When CUR was encapsulated, our data also demonstrated that CUR-loaded T807/RPCNP NPs can relieve AD symptoms by reducing p-tau levels and suppressing neuronal-like cells death both in vitro and in vivo. The memory impairment observed in an AD mouse model is significantly improved following systemic administration of CUR-loaded T807/RPCNP NPs.ConclusionIntravenous neuronal tau-targeted T807-modified novel biomimetic nanosystems are a promising clinical candidate for the treatment of AD.
Highlights
Many therapeutic strategies for Alzheimer’s disease (AD) have been explored, these strategies are seldom used in the clinic
The resultant RBCm were coated onto the surface of NPs through mechanical extrusion to form RBCm-coated PLGA (RPCNP) NPs; these were transferred to water after modification with amino-T807, which was obtained by conjugating amino-T807 to DSPE-PEG-N-hydroxy succinimide (NHS) (Fig. 2a)
Transmission electron microscopy (TEM) revealed that the nanoparticles were successfully coated with RBCm and had a diameter less than 200 nm (Fig. 2d)
Summary
Many therapeutic strategies for Alzheimer’s disease (AD) have been explored, these strategies are seldom used in the clinic. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. We devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau. The complex multifactorial nature of polygenic Alzheimer’s disease (AD) presents challenges for drug development. Numerous studies suggest removing amyloid-β (Aβ) deposits is “a promising therapeutic strategy”, almost all the Aβ-targeting drug candidates. Phosphorylation of tau decreases its affinity for microtubules, thereby decreasing overall tubulin assembly, which leads to the development of intraneuronal neurofibrillary tangles (NFTs) [7]. NFTs are formed from phosphorylated tau aggregates and remain intracellular until the neuron dies [8]. Efficacy can be hindered by both the failure to attain adequate intraneuronal drug concentrations and the occurrence of off-target effects on extraneuronal machinery [12]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
