Engineered Aptamer-Organic Amphiphile Self-Assemblies for Biomedical Applications: Progress and Challenges.

Currently, nucleic acid aptamers are exploited as robust targeting ligands in the biomedical field, due to their specific molecular recognition, little immunogenicity, low cost, ect. Thanks to the facile chemical modification and high hydrophilicity, aptamers can be site-specifically linked with hydrophobic moieties to prepare aptamer-organic amphiphiles (AOAs), which spontaneously assemble into aptamer-organic amphiphile self-assemblies (AOASs). These polyvalent self-assemblies feature with enhanced target-binding ability, increased resistance to nuclease, and efficient cargo-loading, making them powerful platforms for bioapplications, including targeted drug delivery, cell-based cancer therapy, biosensing, and bioimaging. Besides, the morphology of AOASs can be elaborately manipulated for smarter biomedical functions, by regulating the hydrophilicity/hydrophobicity ratio of AOAs. Benefiting from the boom in DNA synthesis technology and nanotechnology, various types of AOASs, including aptamer-polymer amphiphile self-assemblies, aptamer-lipid amphiphile self-assemblies, aptamer-cell self-assemblies, ect, have been constructed with great biomedical potential. Particularly, stimuli-responsive AOASs with transformable structure can realize site-specific drug release, enhanced tumor penetration, and specific target molecule detection. Herein, the general synthesis methods of oligonucleotide-organic amphiphiles are firstly summarized. Then recent progress in different types of AOASs for bioapplications and strategies for morphology control are systematically reviewed. The present challenges and future perspectives of this field are also discussed.