Neuronal mitochondrial dysfunction caused by excessive reactive oxygen species (ROS) is an early event of sporadic Alzheimer's disease (AD), and considered to be a key pathologic factor in the progression of AD. The targeted delivery of the antioxidants to mitochondria of injured neurons in brain is a promising therapeutic strategy for AD. A safe and effective drug delivery system (DDS) which is able to cross the blood-brain barrier (BBB) and target neuronal mitochondria is necessary. Recently, bioactive materials-based DDS has been widely investigated for the treatment of AD. Herein, we developed macrophage (MA) membrane-coated solid lipid nanoparticles (SLNs) by attaching rabies virus glycoprotein (RVG29) and triphenylphosphine cation (TPP) molecules to the surface of MA membrane (RVG/TPP-MASLNs) for functional antioxidant delivery to neuronal mitochondria. According to the results, MA membranes camouflaged the SLNs from being eliminated by RES-rich organs by inheriting the immunological characteristics of macrophages. The unique properties of the DDS after decoration with RVG29 on the surface was demonstrated by the ability to cross the BBB and the selective targeting to neurons. After entering the neurons in CNS, TPP further lead the DDS to mitochondria driven by electric charge. The Genistein (GS)- encapsulated DDS (RVG/TPP-MASLNs-GS) exhibited the most favorable effects on reliveing AD symptoms in vitro and in vivo by the synergies gained from the combination of MA membranes, RVG29 and TPP. These results demonstrated a promising therapeutic candidate for delaying the progression of AD via neuronal mitochondria-targeted delivery by the designed biomimetic nanosystems.

Reactive oxygen species (ROS)-induced neuronal mitochondrial dysfunction is a key pathologic factor in sporadic Alzheimer’s disease (AD). Neuronal mitochondria have been proposed to be a promising therapeutic target for AD, especially for the failures of phase III clinical trials on conventional amyloid-β (Aβ) targeted therapy. However, the efficient intravenous delivery of therapeutic agents to neuronal mitochondria in the brain remains a major challenge due to the complicated physiological environment. Recently, biomaterials-based nanomedicine has been widely investigated for the treatment of AD. Herein, we devised a strategy for functional antioxidant delivery to neuronal mitochondria by loading antioxidants into red blood cell (RBC) membrane-coated nanostructured lipid carriers (NLC) bearing rabies virus glycoprotein (RVG29) and triphenylphosphine cation (TPP) molecules attached to the RBC membrane surface (RVG/TPP NPs@RBCm). With the advantage of suitable physicochemical properties of NLC and unique biological functions of the RBC membrane, RVG/TPP NPs@RBCm are stabilized and enabled sustained drug release, providing improved biocompatibility and long-term circulation. Under the synergistic effects of RVG29 and TPP, RVG/TPP NPs@RBCm can not only penetrate the blood–brain barrier (BBB) but also target neuron cells and further localize in the mitochondria. After encapsulating Resveratrol (RSV) as the model antioxidant, the data demonstrated that RVG/TPP-RSV NPs@RBCm can relieve AD symptoms by mitigating Aβ-related mitochondrial oxidative stress both in vitro and in vivo. The memory impairment in APP/PS1 mice is significantly improved following the systemic administration of RVG/TPP-RSV NPs@RBCm. In conclusion, intravenous neuronal mitochondria-targeted dual-modified novel biomimetic nanosystems are a promising therapeutic candidate for ROS-induced mitochondrial dysfunction in AD.

Phenolic compounds are important constituents of red wine, contributing to its sensory properties and antioxidant activity. Owing to the diversity and structural complexity, study of these compounds was mainly limited, during the last three decades, on their low-molecular-mass compounds or simple phenolic compounds. Only in recent years, much attention has been paid to highly polymerized polyphenols in grape and red wines. The reason for this is largely due to the development of analytical techniques, especially those of HPLC-ESI-MS, permitting the structural characterization of highly polymerized polyphenols. Furthermore, the knowledge on the biological properties of polymeric polyphenols of red wine is very limited. Grape polyphenols mainly consist of proanthocyanidins (oligomers and polymers) and anthocyanins, and low amount of other phenolics. Red wine polyphenols include both grape polyphenols and new phenolic products formed from them during winemaking process. This leads to a great diversity of new polyphenols and makes wine polyphenol composition more complex. The present paper summarizes the advances in the research of polymeric polyphenols in grape and red wine and their important role in Enology. Scientific results indicate that polymeric polyphenols, as the major polyphenols in grape and red wine, play a major role in red wine sensory properties, color stability and antioxidant activities.