RETRACTED ARTICLE: Neuron tau-targeting biomimetic nanoparticles for curcumin delivery to delay progression of Alzheimer’s disease

Abstract

Background: Although 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. Results: Curcumin (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. Conclusion: Intravenous neuronal tau-targeted T807-modified novel biomimetic nanosystems are a promising clinical candidate for the treatment of AD.

Nanomedicine: A Promising Way to Manage Alzheimer’s Disease

“…A stabilized and sustained curcumin delivery across the BBB is also achieved by using a nanoemulsion of red blood cell membranecoated PLGA particles with embedded T807 molecules on the red blood cell membrane surface (T807/RPCNP) loaded with curcumin. Mutual effects of T807, 807/RPCNP exhibit strong inhibitory effects against tau-associated pathogenesis (Gao C. et al, 2020). In another study, hydroxypropylcyclodextrin-encapsulated curcumin complexes (CUR/HP-CD inclusion complexes) emulsion shows greater cellular uptake of curcumin across the BBB and can be considered as a better carrier system to deliver curcumin to the brain for AD therapy (Zhang et al, 2020).…”

Curcumin and Its Derivatives as Theranostic Agents in Alzheimer’s Disease: The Implication of Nanotechnology

“…Synergistic effects of T807, T807/RPCNP showed effective penetration across the blood-brain barrier, and they also exhibited a high binding affinity to hyperphosphorylated tau in nerve cells where they block multiple critical pathways in tau-associated AD pathogenesis. Additionally, curcumin loaded T807/RPCNP nanoparticles could relieve AD symptoms by reducing phosphorylated-tau levels and inhibiting the neuronal death both in vitro and in vivo [ 151 ]. Curcumin nanoformulation by altering the surface of the PLGA polymer and encapsulation of selenium nanoparticles could decrease the Aβ load and inflammations in the brains samples of AD mice and treated the memory loss of the model mice.…”

Nano Carrier Drug Delivery Systems for the Treatment of Neuropsychiatric Disorders: Advantages and Limitations

“…Synergetic action of T807 with triphenylphosphine (TPP) produces an inhibitory effect on key components of AD pathogenesis associated with tau-phosphorylation and prevents neurodegeneration. Thus, the systemic administration red blood cell PLGA nanoparticles loaded with curcumin recover cognitive impairments in the mouse model of AD [ 232 ].…”