Amyloid-Binding Aptamer Conjugated Curcumin–PLGA Nanoparticle for Potential Use in Alzheimer’s Disease

Aptamers as Promising Molecular Recognition Elements for Diagnostics and Therapeutics in the Central Nervous System

“…This was confirmed by transmission electron microscopy imaging. Building on this work, Mathew et al, (2012) conjugated the N2 aptamer to poly(lactic-co-glycolic acid) [PLGA]-coated curcumin nanoparticles [76]. Curcumin is also known to inhibit aggregate formation.…”

“…As suggested by the authors, conjugation of the N2 aptamer to curcumin-PLGA nanoparticles could potentially allow for targeted delivery of curcumin to excess peripheral amyloid. This alternative strategy may be useful in treating AD, as a reduction in peripheral amyloid has been linked with decreased brain amyloid [76].…”

Aptamers

“…Of particular interest are DNA origamis which are created by combining large single-stranded DNA frameworks (e.g., M13 bacteriophage genomic DNA (7249 nucleotides) [147]) with hundreds of shorter (20-60 nucleotides) oligonucleotides (called staple strands) partially complementary to particular sequences on the genomic DNA scaffold so as to form pre-designed two-and/or three-dimensional folds [3,148]. Since both aptamers and DNA origami are made out of the very same biopolymer and because of the inherent binding capacity of aptamers, a combination of both nucleic acid-based materials has been used for different applications including: (1) defined spatial positioning of proteins (and other ligands of interest) on DNA arrays for medical diagnostic, biosensing, or tissue and material engineering purposes [149,150]; (2) development of nanorobots for the delivery of drugs and other payloads [151,152]; and (3) the creation of multimodal sensing platforms [153].…”

“…The authors postulated that the resultant smaller amyloid fragments could easily be cleared by phagocytosis [147]. Interestingly, a recently published review [148] cites the above study, "... the N2 aptamer conjugated to curcumin-polymer nanoparticles enhanced binding to, and disaggregated, amyloid plaques, which were then cleared by phagocytosis", misleading the reader by misreporting that actual "amyloid plaques" were used and "phagocytosis assays" were done in the original study [147]. Taking both studies [126,147] together, it is unclear whether the N2 aptamer or curcumin or both could bind Aβ42 fibrils (not plaques as mentioned [148], which are the in vivo hallmarks of AD) and degrade them because both activities were seemingly attributed to curcumin and N2.…”

“…Interestingly, a recently published review [148] cites the above study, "... the N2 aptamer conjugated to curcumin-polymer nanoparticles enhanced binding to, and disaggregated, amyloid plaques, which were then cleared by phagocytosis", misleading the reader by misreporting that actual "amyloid plaques" were used and "phagocytosis assays" were done in the original study [147]. Taking both studies [126,147] together, it is unclear whether the N2 aptamer or curcumin or both could bind Aβ42 fibrils (not plaques as mentioned [148], which are the in vivo hallmarks of AD) and degrade them because both activities were seemingly attributed to curcumin and N2. Importantly, curcumin along with resveratrol and epigallocatechin-3-gallate (reviewed [149]) have been dubbed as pan-assay-interfering compounds [150,151], and conclusions made about these three polyphenols in the AD literature in relation to their effects on Aβ should be reassessed carefully [152].…”