Aptamer-Nanoconjugates as Potential Theranostics in Major Neuro-Oncological and Neurodegenerative Disorders

This review aims to point out the main achievements in the cutting-edge field of aptamer nanotechnology and its applications in the most frequent neuro-oncological and neurodegenerative diseases. The article discusses the properties, advantages and drawbacks of aptamers (AP), and their design and selection by various SELEX methods, as well as the synergical advantages as theranostics of the aptamer-functionalized nanoparticles (Ap-NP). The Ap-nanoconjugates properties are compared to those of Ap and unconjugated NP. Moreover, the article comparatively analyzes the aptamer-based approaches vs. antibody-drug conjugates vs. exosome-based delivery systems vs. unconjugated NP, as targeted therapies in neurodegenerative diseases and gliomas. The review presents major challenges in Ap-NP conjugates' clinical progress (concerning the in vivo enzymatic stability, blood-brain barrier (BBB) permeability, selective intracellular uptake in the brain parenchyma and target tissues, rapid renal clearance, off-target toxicity, immunogenicity, reproductible manufacturing) and the investigated developmental strategies to solve them. Furthermore, relevant examples and comparative insights regarding preclinically tested Ap and Ap-NP conjugates are presented for targeted delivery systems loaded with chemotherapeutical drugs or genes, Ap-siRNA chimeras and immunotherapeutical aptamers, which are evaluated in glioblastomas (GBM), amyloidogenic diseases and multiple sclerosis (MS); radiotherapy enhancers in GBM; aptasensors for diagnostic and bioimaging-guided therapy in GBM, MS and amyloidopathies. The review finally points out future research directions in order to accelerate the clinical translation and the real-world impact as theranostics of the most preclinically advanced Ap-NP conjugates in major neuro-oncological and neurodegenerative disorders.