[Preparation of dual-functional composite magnetic nanomaterials modified with different metals/aptamers and their performance in exosome enrichment].

Exosomes, which are extracellular vesicles with sizes of 30-150 nm, contain proteins, lipids, RNA, etc., which can reflect important information about parental cells. They also have unique structures and can perform characteristic biological functions. Although the release of exosomes is a normal process, tumor cells release more exosomes, and the contents can induce cancer progression. Exosomes are widely distributed in body fluids at high concentrations and are easy to obtain; hence, the collection of exosomes released by tumor cells has become one of the main directions in tumor liquid biopsy. In order to ensure the reproducibility and consistency of liquid biopsy results, it is necessary to develop methods for enriching exosomes in sufficient yield and purity from complex samples. Based on the size, hydrophobic proteins, and characteristic proteins of exosomes, various methods for exosome separation and purification have been developed, such as ultracentrifugation, polymer precipitation, and immunoaffinity methods. An aptamer (Apt) is an oligonucleotide chain with a total length of 20-100 nt, which has ligand binding properties and can be used to detect different types of drugs and biomolecules at the nanomolar level. Characteristic proteins on the surface of exosomes such as CD63, CD9, and CD81 are often used as exosomes markers. At present, a variety of aptamer sequences targeting the characteristic proteins of exosomes have been reported. Zirconium and titanium cations as well as the oxides of these metals show high affinity to the phospholipid bilayer on the exosome surface and are used in the separation and purification of exosomes. Metal organic frameworks (MOFs) can provide a wealth of metal oxide affinity sites to interact with the phospholipid bilayer membrane, and their diverse organic ligands can provide numerous modification sites to bind with aptamers. In this study, different metal/aptamer dual-functional composite magnetic nanomaterials were prepared by exploiting the surface chemistry and biological characteristics of exosomes for the enrichment and purification of exosomes. Because of the specific affinity of the aptamers toward the target membrane protein on the exosome surface and the affinity of the titanium or zirconium oxide toward the phospholipid bilayer membrane of exosomes, dual-functional magnetic nanomaterials can greatly improve the enrichment capacity and separation selectivity of exosomes. Fe