PLGA Nanoparticles Modified With Targeting Peptide Inhibit A? Generation And Attenuate Memory Deficits In Alzheimer's Disease Mice

Alzheimer's disease(AD)is considered as an "urgency" for public health,since it represents one of the most dramatic causes of death in adults.,characterized by senile plaquesand neurofibrillary tangles and the abnormal aggregates of amyloid ?(A?)peptides in the brains of AD patients.Conventional strategies failed to treat AD in clinical trials,partly due to the poor solubility,low bioavailability and ineffectiveness of the tested drugs to cross the blood-brain barrier(BBB).Nanocarriers have been studied and investigated in order to ameliorate the detection(in vitro and in vivo)and the therapeutic options in AD.Here,we designed a novel kind of poly lactide-co-glycolic acid(PLGA)nanoparticles by loading with AP generation inhibitor S1 and curcumin to target the detrimental factors in AD development and by conjugating with brain targeting peptide CRT,an iron-mimic peptide that targets transferrin receptor(TfR),to improve BBB penetration.The average particle size of PLGA nanoparticles and CRT-conjugated PLGA nanoparticles were 128.6 nm and 139.8 nm,respectively.The curcumin encapsulation efficiency(EE%)of PLGA nanoparticles with or without CRT peptide were 23.2 ± 5.3%and 21.4 ± 6.9%,and the curcumin loading capacity(LC%)were 0.54 ± 0.04%and 0.42 ± 0.06%,respectively.Our Y-maze and new object recognition test results demonstrated that the PLGA nanoparticles significantly improved the spatial memory and recognition in transgenic AD mice.The treatment by PLGA nanoparticles significantly decreased the level of A?,reactive oxygen species(ROS),TNF-a and IL-6,and enhanced the activities of super oxide dismutase(SOD)and synapse number.Our results also showed that CRT-NP-S1+Cur exhibited most beneficial effect on the treatment of AD mice,suggesting that CRT peptide,S1,and curcumin exerted their corresponding functions during treatment.