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

Abstract

Moreover, the characteristic of being nucleic acid molecules provides aptamers with additional distinctive properties: 1) easy modification with a variety of functionalities in a controllable manner; 2) sequence-specific hybridization via Watson−Crick base pairing; 3) conformational changes induced by specific molecular interactions between target and aptamer. All these features make aptamers promising targeting ligands for biomedical applications. Currently, by combining the advantages of nanotechnology and DNA synthesis technology, a wide range of aptamer-functioned nanomaterials have been designed, including 2D nanosheets, gold nanoparticles, liposomes, polymer nanoparticles, DNA nanostructures, which exhibit great potential in bioimaging, biosensing, gene therapy, and targeted drug delivery. [3] Among the aptamer-functionalized nano-systems, aptamer-organic amphiphile self-assemblies (AOASs) have received increasing attention in biomedical field, due to their unique advantages. [4,5] Aptamer-organic amphiphiles (AOAs), prepared by covalently conjugating organic moieties to hydrophilic aptamers, are building blocks to form AOASs via noncovalent driving forces like hydrophobic interactions, hydrogen-bonding, electrostatic interactions, van der Waals forces, and Watson−Crick base pairing. [6,7] The spontaneously shaped AOASs normally have small sizes (10-100 nm) and low critical micelle concentrations (CMCs), which are favorable for tumor accumulation through enhanced permeability and retention (EPR) effect. [8] Generally, AOASs are coreshell nanostructures, where the core and shell are aggregated hydrophobic segment and aptamer corona, respectively. The hydrophobic core can be used to carry multiple water-insoluble compounds, making AOASs serve as versatile carriers for cargo delivery. [9] The aptamer corona renders AOASs with several intriguing merits. First, the high density of aptamers outside endows AOASs with enhanced target binding affinity, called multivalent effect. [10] In addition, the close packing of nucleic acid strands of AOASs can predominantly increase the resistance to nuclease, which is always a big challenge for nucleic acid-based materials. It is speculated that the steric hindrance and a dense anion generated from the close packing of nucleic acid strands could hinder the access of nuclease 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, cellbased cancer therapy, biosens...

Recent Advances in CRISPR/Cas-Based Biosensors for Protein Detection

“…Due to the large molecular mass, high immunogenicity, and batch-to-batch variations of antibodies, the reliability and repeatability of antibody-based CRISPR biosensors may vary for each test, limiting their applications in protein detection. In the last decades, nucleic acid aptamers (simplified aptamers) have received the widespread attention of scientists, thanks to their excellent performance in sensing platforms, low cost, and comparable sensitivity [ 64 ]. Aptamers are synthetic functionalized single-stranded oligonucleotide sequences (DNA and RNA), also known as chemical antibodies, which are specific nucleic acid sequences and have three-dimensional structures, allowing them to bind target molecules with high affinity and specificity [ 65 , 66 ].…”

pH/Thermal-Sensitive Nanoplatform Capable of On-Demand Specific Release to Potentiate Drug Delivery and Combinational Hyperthermia/Chemo/Chemodynamic Therapy

“…The tumor regions show slightly low pH values (∼5.5), which provoke structural distortion and disassembly of pH-responsive carriers. , Although pH-sensitive materials have been widely studied in cancer therapy, the insufficient responsive rate and regulation capacity of drug release remain a major hurdle that impedes the therapeutic efficiency. Consequently, it is desirable to develop an intelligent nanoplatform that combines pH-responsive polymers and other stimuli-responsive materials to efficiently regulate its functional payload release in a controlled manner. , For this purpose, thermo-sensitive materials which have been extensively applied in smart drug-delivery systems may be an ideal choice. When heated above the average transition temperature ( T m), the thermo-responsive nanoplatforms can deform significantly and enhance the encapsulated drug release. , Thereby, the introduction of thermo-responsive substances can remedy the defect of poor responsiveness in pH-responsive drug release and render the nanoplatforms with the desired temporal, spatial, and dosage controllabilities in drug delivery.…”

“…Consequently, it is desirable to develop an intelligent nanoplatform that combines pH-responsive polymers and other stimuli-responsive materials to efficiently regulate its functional payload release in a controlled manner. 15,16 For this purpose, thermo-sensitive materials which have been extensively applied in smart drug-delivery systems may be an ideal choice. When heated above the average transition temperature (Tm), the thermo-responsive nanoplatforms can deform significantly and enhance the encapsulated drug release.…”

In Situ Measurement of ATP in Single Cells by an Amphiphilic Aptamer-Assisted Electrochemical Nano-Biosensor

“…Because of their simple operation, low immunogenicity, and low cost, aptamers have become a powerful targeting ligand. 16 At present, many aptamer-based electrochemical sensors have been developed. 17 Due to its high hydrophilicity and simple chemical modification, aptamers can be site-specifically ligated with hydrophobic fractions to prepare aptamer−organic amphiphiles (AOAs).…”

“…Among them, aptamers are single-stranded oligonucleotides that specifically bind to target molecules. Because of their simple operation, low immunogenicity, and low cost, aptamers have become a powerful targeting ligand . At present, many aptamer-based electrochemical sensors have been developed .…”