| Tumor has become one of the main diseases that threaten human life in today's society.It has the characteristics of difficult healing and high mortality.The small molecule chemical drugs currently used in the chemotherapy of tumor treatment often have disadvantages such as large side effects and poor water solubility,which improves the difficulty of tumor treatment.Therefore,the development of a new type of drug that can solve the above problems has become a top priority,but the development of new drugs is costly and time-consuming.In order to solve these problems better and faster,drug carrier materials have emerged.Polypeptides have become a new drug carrier material favored by researchers because of their good biocompatibility and degradability.Amphiphilic polypeptides can spontaneously form self-assemblies in aqueous solution due to their unique sequence,such as micelles,nanofibers and vesicles,etc.,among which polypeptide nanomicelles having a unique "shell-core" structure have been widely used as carriers for antitumor drugs in the biomedical field.In view of the current situation of poor anti-tumor drugs with poor water solubility and large side effects,small molecule polypeptides with self-assembly properties are used as carriers for the delivery of the antitumor drug doxorubicin(DOX)in order to enhance the solubility of drugs and improve drugs.The controlled release and tumor targeting performance have important theoretical significance and application value.In this thesis,an amphiphilic small molecule polypeptide(FFHFFH-KKGRGD,P12)was designed and prepared by solid phase synthesis,which drives self-assembly in aqueous solution by hydrogen bonding and hydrophobic interaction to form a "core-shell" structure with entrapment ability.This structure can entrap the poorly water-soluble antitumor drug DOX to form a peptide-loaded DOX nanomicelle(P12&DOX)for tumor treatment.Dox-loaded micelles were prepared by dialysis method,the method was simple and easy.The encapsulation efficiency(46.2%)and drug loading(26.4%)of the prepared nano-micelles were higher than those of the products prepared by solvent evaporation method,the encapsulation efficiency and drug loading were 28.8%and 18.0%,respectively,and the prepared nanoparticles were uniform in size and small in particle size,and the average particle diameter was only 120 nm,which was smaller than 170 nm prepared by solvent evaporation method.Through many loading experiments,the optimum feed ratio of Pi2-DOX was determined to be P12:DOX=4:1.The release of nano-micelles was observed by simulating the human micro-environment.The results showed that the nano-system has certain acid-sensitive properties.Compared with the release effect of commercially available doxorubicin,the P12&DOX nano-micelles have certain sustained release ability.The cytotoxicity of P12,P12&DOX and DOX was detected by CCK-8 method.It was proved that P12 has good biocompatibility and has certain modification effect on doxorubicin,which reduces its damage to normal cells.The uptake of nano-micelles by normal cells(HUVEC)and tumor cells(4T1)was observed by laser confocal microscopy.The results showed that 4T1 cells had more uptake of P12&DOX nano-micelles than HUVEC cells;nano-micelles can accumulate around the tumor tissue for a longer period of time,and the released drug can cause more effective killing of the tumor cells.The flow cytometry quantitatively observed the uptake and efflux of the drug-loaded particles,and further explored the feasibility of P12&DOX nano-micelles as an anti-tumor drug-loading system. |
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