Polymer nanoparticles, or polymer nanoparticles, have a particle size range of 1 ~ 1000nm, which can be obtained by various methods such as microemulsion polymerization. This kind of particle has a large specific surface area, and some new properties and functions that ordinary materials do not have appear.
At present, the application of nano-polymer materials has been involved in many aspects, such as immunoassay, drug controlled release carrier and human diagnosis and treatment. Immunoassay, as a routine analytical method, has played a great role in the quantitative analysis of protein, antigens, antibodies and even whole cells. According to different markers, immunoassay can be divided into fluorescence immunoassay, radioimmunoassay and enzyme-linked immunoassay. The immunoaffinity molecular markers corresponding to the analyte are fixed on a specific carrier in the form of valence bonds, the solution containing the analyte is incubated with the carrier, and then the amount of free carrier is detected by a microscope, so that the analyte can be quantitatively analyzed accurately. The selection of carrier materials is very important in immunoassay. Polymer nanoparticles, especially those with hydrophilic surfaces, have been widely used as new labeling carriers because of their low adsorption capacity for nonspecific protein.
Polymer nanoparticles have important application value in drug controlled release. Many research results have confirmed that some drugs can only exert their efficacy in specific parts, and are easily decomposed by some biological macromolecules in digestive juice. Therefore, the efficacy of oral administration of such drugs is not ideal. So people use some biodegradable polymer materials to protect drugs and control the release rate of drugs. These polymer materials usually exist in the form of microspheres or microcapsules. After the drug is carried and transported, the drug effect is little damaged, and the release of the drug can be effectively controlled, thus prolonging the action time of the drug. Polymer materials as drug carriers mainly include polylactic acid, lactic acid-glycolic acid polymer, polyacrylate and so on. Drug carriers and various drugs made of nano-polymer materials, whether hydrophilic or hydrophobic or biomacromolecule preparations, can load or coat a variety of drugs, and can effectively control the release rate of drugs.
For example, Central South University has carried out research on the treatment of liver cancer with magnetic nanoparticles of "nano-missiles", which target drugs at the focus. The research contents include the magnetic targeting of magnetic adriamycin albumin nanoparticles in normal liver, the distribution in rats and the therapeutic effect on transplanted liver cancer in rats. The results show that magnetic adriamycin albumin nanoparticles have high magnetic targeting, and their aggregation in transplanted liver tumors in rats is obviously increased, which has a good therapeutic effect on transplanted tumors.
The research of targeting technology is mainly carried out at two levels: physical and chemical orientation and biological orientation. Physical and chemical orientation lacks accuracy in practical application, and it is difficult to ensure that normal cells are not attacked by drugs. Bioguidance can solve the problem of targeted drug delivery at a higher level. Physico-chemical targeting system uses the characteristics of pH sensitivity, thermal sensitivity and magnetic sensitivity of drug carriers to deliver drugs to tumor tissues under the action of external environment (such as external magnetic field). The targeting of magnetic nanocarriers in organisms is to enrich magnetic nanoparticles in diseased parts by using external magnetic field, so as to reduce the exposure of drugs in normal tissues, reduce toxic and side effects and improve the curative effect of drugs. Magnetically targeted nano-drug carriers are mainly used to treat malignant tumors, cardiovascular diseases, cerebral thrombosis, coronary heart disease, emphysema and other diseases. Biological targeting system utilizes the specificity of antibodies, cell membrane surface receptors or specific gene fragments to bind ligands to carriers and specifically bind with antigen recognizers on the surface of target cells, so as to accurately deliver drugs to tumor cells. The targeted release of drugs (especially anticancer drugs) is facing the problem of non-selective clearance of reticuloendothelial system (RES). In addition, most drugs are hydrophobic, and precipitation may occur when they are coupled with nanoparticle carriers. Using polymer gel as drug carrier is expected to solve this problem. Because this gel can be highly hydrated, it can be used to enhance the penetration and retention of cancer cells if its size reaches nanometer level during synthesis. At present, although many protein and enzyme antibodies can be synthesized in the laboratory, better and more specific targeting substances need to be researched and developed. In addition, it is necessary to study the combination of drug carriers and targeted substances.
This kind of technology needs more reliable nano-carriers, more accurate targeting substances, more effective therapeutic drugs, more sensitive and convenient sensors, as well as dynamic testing and decomposition methods of the mechanism of the carrier in vivo, in order to be safely and effectively applied to clinic.
DNA nanotechnology refers to nanotechnology designed according to the principle of physical and chemical characteristics of DNA, which is mainly used in molecular assembly. Simplicity of bases, constancy and specificity of complementary rules, diversity of genetic information, conformational specificity and topological targeting embodied in DNA replication are all design principles needed by nanotechnology. Now the self-assembly of nanoparticles can be realized by using biological macromolecules. A single-stranded DNA fragment is attached to the surface of gold nanoparticle A with a diameter of 65438±03nm, and another single-stranded DNA fragment with complementary sequence is attached to the surface of gold nanoparticle B. When A and B are mixed, A and B will be automatically linked together in the case of DNA hybridization. The self-assembly of nanoparticles can be realized by using the complementary characteristics of DNA double strands. Self-assembly of biological macromolecules has a significant advantage: it can provide highly specific binding. This is necessary for the self-assembly of complex systems.
PD-loop developed by Bukanov, Institute of Biomedical Engineering, Boston University, USA (embedding an oligopeptide sequence in double-stranded linear DNA) has greater advantages than PCR amplification technology. Its primers don't need to keep the complete biological activity state, and its product sequence specificity is high, unlike PCR products, which may be mismatched. The birth of PD loop opens up a new way for linear DNA oligonucleotide hybridization technology, which makes it possible to screen and separate special DNA fragments from complex DNA mixtures and may be applied to DNA nanotechnology.
Gene therapy is a great progress in therapeutics. Plasmid DNA can repair genetic errors or produce therapeutic factors (such as polypeptide, protein, antigen, etc. ) after being inserted into the target cell. Using nanotechnology, DNA can be located in cells through active targeting; Plasmid DNA is concentrated to 50 ~ 200 nm and negatively charged, which is helpful for it to invade the nucleus effectively. Whether plasmid DNA can be inserted into nuclear DNA depends on the size and structure of nanoparticles: nanoparticles at this time are composed of DNA itself, but their physical and chemical characteristics need further study.
Liposome (1 liposome) is a drug carrier with fixed time, which belongs to a new dosage form of targeted drug delivery system. In 1960s, British A.D.Banfiham first discovered that phospholipids dispersed in water formed a closed vesicle composed of lipid bilayer, which contained water phase. Bimolecular vesicles with similar biofilm structure and permeability formed by bimolecular phospholipids suspended in water are called liposomes. In the early 1970s, Y.E.Padlman and others used liposomes as carriers of bacteria and some drugs for the first time on the basis of biofilm research. Nanoliposomes as drug carriers have the following advantages.
(1) is composed of water-phase vesicles wrapped by phospholipid bilayer, which is different from various solid microsphere drug carriers. Liposomes have high elasticity and good biocompatibility.
(2) It has wide adaptability to the drugs it carries. Water-soluble drugs are loaded in the internal water phase, fat-soluble drugs are dissolved in the lipid membrane, amphiphilic drugs can be inserted into the lipid membrane, and the same liposome can contain both hydrophilic and hydrophobic drugs.
(3) Phospholipid itself is a component of cell membrane, so nano-liposomes are nontoxic when injected into the body, with high bioavailability and no immune response.
(4) Protect the contained drugs to prevent them from being diluted by body fluids and destroyed by enzymes in the body.
Nanoparticles can make the drug transport in human body more convenient, and modify the surface of liposomes, such as assembling various ligands with selectivity or affinity for specific cells on the surface of liposomes, in order to find the target. Taking the liver as an example, the nanoparticle-drug complex can achieve the targeting effect in both passive and active ways; When the complex is captured and swallowed by Kupffer cells, the drug accumulates in the liver, and then gradually degrades and releases into the blood circulation of human body, which increases the drug concentration in the liver and reduces the side effects on other organs, which is a passive targeting effect; When the size of nanoparticles is small enough, about 100 ~ 150 nm, and the surface is covered with a special coating, they can escape the phagocytosis of kupffer cells, and the substances such as monoclonal antibodies connected with them are located in liver parenchymal cells to play a role, which is active targeting. Smart drugs wrapped in several layers of nanoparticles can actively search and attack cancer cells or repair damaged tissues after entering the human body.
Encouragingly, nanoparticles are used as carriers to transport peptides and protein drugs, not only because nanoparticles can improve the pharmacokinetic parameters of peptide drugs, but also effectively promote peptide drugs to penetrate the biological barrier to some extent. Nanoparticle drug delivery system, as a tool to develop peptides and protein drugs, has a very broad application prospect.
Nano-particles have a large number of free surfaces due to their small particle size, high colloidal stability and excellent adsorption performance, and can quickly reach adsorption equilibrium. Therefore, polymer nanoparticles can be directly used for adsorption and separation of biological substances. Nano-particles are pressed into thin sheets to make filters, which can be used for serum disinfection in pharmaceutical industry (the size of viruses causing human diseases is generally tens of nanometers) because the filtering pore size is nano. By introducing carboxyl, hydroxyl, sulfonic acid, amino and other groups on the surface of nanoparticles, nanoparticles can interact with biomacromolecules such as protein and nucleic acid through electrostatic or hydrogen bonding, resulting in the sedimentation of biomacromolecules, thus achieving the purpose of separating biomacromolecules. When conditions change, biomacromolecules can be desorbed from nanoparticles and can be recovered.
Nanopolymer particles can also be used for interventional diagnosis and treatment of some difficult diseases. Because nanoparticles are much smaller than red blood cells (6 ~ 9 microns) and can move freely in the blood, they can be injected into various parts of the human body to check the lesions and treat them. According to reports, the results of animal experiments show that lactate-glycolic acid * * * polymer nanoparticles loaded with dexamethasone can effectively treat arterial restenosis, and lactate-glycolic acid * * * polymer nanoparticles loaded with antiproliferative drugs can effectively prevent coronary restenosis by coronary artery administration; In addition, nano-polymers loaded with antibiotics or anticancer agents can be transported into the body through arteries and used for clinical treatment of certain organs. Nanospheres loaded with drugs can also be made into emulsions for parenteral or enteral injection; It can also be made into vaccine for subcutaneous or intramuscular injection.