Alzheimer\’s disease (Alzheimer\’s disease, AD) is a degenerative disease of the central nervous system, is the most common type of dementia, mainly by progressive memory impairment, cognitive impairment and languages neurological disorders, psychiatric symptoms, typical pathological feature is extracellular amyloid beta] (amyloid-β, Aβ plaques) formed by deposition of senile plaques, intracellular neurofibrillary tangles and brain atrophy. Since the blood-brain barrier (Blood-Brain Barrier, BBB) hinders most drugs to reach the brain, brain effective drug delivery has been a major challenge for AD and other brain diseases. In order to improve BBB permeability, scientists have developed as BBB penetrating peptides (CRTIGPSVC, CRT), selective targeting CD47 glycoprotein modulators and microglia (Necrostatin-1s, Nec-1s), etc. endogenous transport mechanisms; however, penetrating peptide low transport capacity, Nec-1s poor water solubility and low bioavailability and brain defects brought great difficulties to the study. Recently, Institute of Process Engineering Liu Ruitian and Lu Shuai team developed a new type of poly (lactic acid – glycolic acid) (PLGA) copolymer nanoparticles (CRT-CD47-NP-Nec-1s), through which reactive oxygen species (ROS) responsive to the phenylboronic acid ester bond conjugated CD47 extracellular domain, [ 123] show, \”Do not eat me\” signal , and CRT and Nec-1s wrapped in one. Found high levels of mouse brain ROS cause release of CD47 nanoparticles, resulting granules effectively resident microglial phagocytosis, engulfed Nec-1s may be adjusted to pathological advantageous microglia state, reduce Aβ plaque burden, the proliferation of microglia and astrocytes proliferation, reduce oxidative stress and cytokines AD brain of mice, and ultimately reduce synaptic loss and cognitive impairment therapeutic effect. The study is the first demonstration, the condition for the release of \”Do not eat me\” CD47 signal significantly promoted microglial cells targeted drug delivery, worthy of further research and development of drugs to treat AD. This studyEntitled to the results of \”A Conditionally Releasable\” Do not Eat Me \”CD47 Signal Facilitates Microglia-Targeted Drug Delivery for the Treatment of Alzheimer\’s Disease\” published in the paper \” Advanced Functional Materials \”. As shown, the first wrapping Nec-1s into the copolymer by NPs nanoprecipitation 1, CRT and then respectively NPs surface CD47, and benzene boronic acid conjugate prepared CRT-CD47-NP-Nec- 1s, TEM spectra showed CRT-CD47-NP-Nec-1s from about 70 nm uniform spherical size.
developed by the Institute of CRT-CD47-NP-Nec-1s by preventing phagocytic cells, effectively prolonging its circulation in blood half-life, and CD47 synergistically enhances CRT and its distribution in the brain, being swallowed Nec-1s may be adjusted pathological state advantageous to microglia, by reducing plaque burden and Aβ repair of damaged neurons to save the synaptic loss and cognitive impairment. This microglia targeted drug delivery nanoparticles are expected to be used to explore the role of microglia in AD pathogenesis is of great significance for the research and development of therapeutic AD drugs. The full text link: https: //doi.org/10.1002/adfm.201910691