Gene therapy and oligonucleotide drugs can alleviate or cure many diseases that cannot be treated by traditional methods, especially those caused by genetic defects or abnormalities. Naked nucleic acids are easily degraded by enzymes in tissues or cells, and the cellular uptake is poor, so scientists are working on developing delivery vehicles to transport nucleic acids. Viral vectors can effectively infect host cells and have become the most popular vectors for gene transfer. However, viral vectors have high cytotoxicity and immunogenicity, are prone to inflammatory reactions, and have problems such as high cost, limited size and quantity of loaded DNA. In recent years, nanoparticles have been extensively studied as nucleic acid carriers.
Nanoparticles are granular dispersions or solid particles with a particle size in the range of 10-1000nm, which can be used for delivery to obtain enhanced permeability and retention (EPR). It's higher potential and specific surface area make the nucleic acid load larger, and it can also protect nucleic acid molecules from enzymatic degradation and immune recognition. Compared with other carriers, it has higher transport efficiency across cell membranes. In addition, nanocarriers usually have good biocompatibility and even biodegradability, they have little effect on cell growth and metabolism.
Drugs can be incorporated into organic nanoparticles by chemical bonding or physical entrapment. Typical organic nanoparticles include liposomes, nanoemulsions, dendrimers and polymer nanoparticles.
Lipid Nanoparticles (LNPs)
Current lipid-based systems mainly include liposomes, micelles, emulsions, and solid lipid nanoparticles (SLNs). Liposomes are composed of phospholipids, which readily form closed lipid bilayers in aqueous solvents to form nanoscale particles. Liposome nanocarriers have been widely used in the research of oligonucleotide drugs, especially antisense oligonucleotides (ASO) and siRNA. Liposomes include positive, neutral, and negative liposomes, with positive liposomes commonly used as delivery vehicles because they can interact with negatively charged phosphate groups present in nucleic acids through electrostatic forces to form nanoparticles. This lipoplex protects the genetic material within it from degradation and is delivered within mammalian cells.
Polymeric Nanoparticles (PNP)
Typically, polymeric nanoparticles have positively charged units that bind electrostatically to nucleic acids to form multimeric complexes at physiological pH to facilitate gene delivery. In addition, covalent attachment of nucleic acids to polymers can also be achieved through the use of degradable linkers.
Inorganic Nanoparticles
Inorganic nanoparticles (INPs) are synthesized from inorganic particles and biodegradable polycations. Typical inorganic nanoparticles include metals, metal oxides, carbon materials, and magnetic nanoparticles consisting of superparamagnetic iron oxide nanoparticles (SPION). More commonly used are mesoporous silica nanoparticles (MSN), which have properties such as homogeneous pore channels, easy functionalization, biocompatibility, high specific surface area, large pore capacity and biodegradability.
Metal Nanoparticles
The structure of metal nanoparticles as a gene carrier usually uses metal as the core and functional materials as the shell. It has good biocompatibility, storage stability, easy preparation, multi-functionality, and low toxic and side effects. Materials with gene delivery properties gain targeting, controllability, and imageability. However, metal nanoparticles are not easy to degrade in the body, and the safety hazards limit their clinical application.
Inorganic Non-Metallic Nanomaterials
Some gene carriers are obtained by hybridizing inorganic non-metallic nanomaterials with functional molecules, including carbon materials and silicon materials. The biosafety of inorganic non-metallic nanoparticles is better than that of metal nanoparticles, and the functional molecules modified on them are usually better than the functional molecules themselves in terms of transfection efficiency, but the biodegradability of inorganic non-metallic nanoparticles still needs to be improved.
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