| BackgroundCancer is one of the three most common human diseases,as the second killer,the high mortality rate. In the current clinical treatment of cancer, chemical anti-cancer drugs still play a very important role, but these chemotherapy drugs still exist some difficult to overcome the toxicity,side effects,hinder its application. At present, in order to overcome the side effects of small molecules of chemical medicine,nano-delivery system is hot. However, the current drug delivery system is generally only delivery drug to the blood or cytoplasm, it is unknown the next drug go.However, many anticancer drugs work only after entry into the nucleus, requiring precise delivery of the vector to the target site. In addition, anti-cancer drugs themselves kill cancer cells at the same time also have more or less on the normal cell effect, so as to bring great suffering to patients.Drug Delivery System intelligently deliver drug molecules to the lesion site can reduce medication and side effects will be cut back patient pain. Targeted drug delivery system can make the drug concentration and located in the lesion location,then reduce the toxic side effects, with positioning accumulation, trace efficient and so on. Folate receptor is found in some tumor cell over expression molecules, folic acid molecules for the human body normally required substances.AimIn this study, we designed the nano-system based on the living environment of the cells and the specificity of the cytoplasm of the cells. The folate receptor was specifically expressed by the cancer cells as the starting point, and coupled with the folic acid molecules, which made the nano-meter system have directly during the cycle.Firstly,CS/PAA particles with small particle size were prepared and SN-38 was dissolved in water by physical adsorption. Due to work before the preparation of nanoparticles with passive targeting, active search target ability is not strong.Therefore, double-layer granules were prepared and conjugated with folic acid on one of the outer granular materials,which could be used as a targeting agent. The entire nano-system thanks to the ingenious choice of materials, with step-by-step release,accurate delivery function. First, the outer particles released in the acidic cytoplasmic environment, and then small particles into the nucleus in the nuclear environment to release SN-38, intelligent delivery of drugs to the site of action.MethodsPreparation and characterization: The particle size of the inner layer was prepared by dropping method and dropping speed. SN-38 was used as the physical adsorbent. Through transmission, scanning, particle size analysis showed that the inner layer of small particles 20nm, for the uniform smooth spherical structure.XRD showed that folic acid was bound to cmCHI by ionic bonding. According to the principle of double emulsification, the double layer particles were synthesized and characterized by a series of characterization.Biological effects: The WST-1 kit was used to detect the cytotoxicity and material safety of the free drug, the inner and outer layer particles and the double-layer particles of folic acid. Annexin V-FITC/PI kit detection of apoptosis,supporting material safety.Cell uptake: The double-layer granule location and pathways were identified by fluorescence counterstaining. The migration of the whole system was observed by laser confocal microscopy according to the principle of color superposition.ResultThe inner particle is about 20nm,which is a uniform spherical shape. The double-layer particles are 170nm, uniform spherical, and folic acid is bound by ionic bonds. The encapsulation of core-shell nanoparticles reached 86.91% and drug loading was 1.32%. Transmission electron microscopy and fluorescence microscopy confirmed that small particles have been included in the large particles. Outer particles due to the acidic response of PLGA, in the cytoplasm of the acidic environment of the release of small particles under rupture. The swelling reaction of poly acrylic acid under neutral condition and alkaline condition was released, and SN-38 was released by desorption. The entire nanosystem has a sharp pH sensitivity,and the addition of FA can lead the nanosystem to the periphery of cancer cells.The result of WST-1 showed that the selected materials had no toxic effect.Annexin V-FITC/PI test showed that some of the cell death forms were mild apoptotic.Cytotoxicity results showed that the cell viability of A549/Hela cells was the lowest in the two cell lines, which was higher than that in the free drug group, and the cytotoxicity was more significant in Hela cells.Confocal microscopy showed that CS/PAA/SN-3 8 particles were first released from the outer layer of the nanosized system, and then the small particles. diffused into the nucleus.After the nucleation, the SN-38 desorption is free in the nucleus with the swelling reaction.Conclusion:This topic is devoted to accurate nuclear delivery of drugs to overcome SN-38 shortcomings,improve drug utilization,reduce patient suffering. First of all,active targeting of folic acid cancer cells,and then as a sharp acid-base material sensitivity,respectively, in the corresponding acid-base conditions, timely release or release their respective swollen carriers. Indicating that such nano-systems are of significance in nuclear delivery. |
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