Receptor specific, stimuli responsive and subcellular targeted approaches for effective therapy of Alzheimer: Role of surface engineered nanocarriers.

The present review deals in-depth with the current application of nanotechnology in targeting the major pathological hallmarks of Alzheimer's disease. This review further focuses on the surface modification of the nanocarriers using antibody, aptamers, proteins and peptides for specific targeting in the brain by overcoming the biological barriers such as blood brain barrier. The stimuli responsive/pulsatile drug delivery nanoplatforms using stimuli such as pH, temperature, photo-thermal, reactive oxygen species, ultrasonic stimulation and electrical stimulation, which help to create a micro-environment to either trigger the site-specific drug release from the nanoplatform or to reduce the disease burden in the brain, have been discussed. The targeting of nanoplatforms to sub-cellular compartments such as mitochondria, nuclei, endoplasmic reticulum, golgi apparatus and lysosomes along with receptor specific interactions such as such folate, lactoferrin, transferrin, insulin and low-density lipoprotein (LDL) receptors has been included to give reader an idea about strategies to enhance cellular co-localization and receptor based targeting of nanoparticles to enhance efficacy of delivery platform. This article describes the various type of nanoplatforms which include lipidic nanoplatforms, polymeric nanoplatforms, inorganic nanoplatforms (metallic nanocarriers, quantum dots, ceramic based nanocarriers), carbon based nanocarriers and cell derived or biomimetic (exosomes and virus based) nanoplatforms, to either deliver the active ingredient or to themselves target the Alzheimer's disease pathology. Thus the review gives a detailed insight of all the recent research studies carried out using nanotechnology in the field of Alzheimer's disease.