Research And Application Of Controlled Drug Release System Based On Organic Moleculars Self-assemblies

Organic molecules self-assembly carriers are nanocarriers that can be loaded drugs by π-π self-assembly of organic small molecules.As drug carriers,they have been widely used in the diagnosis and treatment of tumors,and they have great potential application and research value.The main research of this paper was focused on the novel self-assembly carriers,which were based on π-π self-assembly of hydrolyzed a-lactalbumin and organic drug molecules,and their application in controlled drug release systems.The paper mainly includes three chapters:In the first chapter,the development,preparation methods and application of nano drug carriers and organic nano drug carriers in biology were introduced in detail.At the same time,the research purpose and content of this paper are briefly described.In the second chapter,two kinds of drug delivery systems based on the self-assembly of the hydrolyzed α-lactalbumin amphiphilic peptides and hydrophobic drug molecules were constructed,(1)The amphiphilic peptides and photosensitizer molecule Chlorin e6(Ce6),hydrophobic Mn3O4 particles were self-assembled into Mn3O4-Ce6-LA nanospheres,then adsorbed doxorubicin(DOX)on the particle surface and modified the target molecule RGD,the Mn3O4-Ce6-LA-DOX-RGD nanocomposite particles were gained.Experimental results show that Mn3O4-Ce6-LA-DOX-RGD nanocomposite particles can target cancer cells.Under the double stimulus of low pH and high glutathione in tumor microenvironment,the composite particles dissociate,release drugs and Mn2+,achieve the integrated role of chemotherapy and MIR imaging;while under light irradiation,Ce6 can produce singlet oxygen for photodynamic therapy.Therefore,the drug delivery system is a multifunctional drug release system integrating chemotherapy,photodynamic therapy,MIR imaging,targeting and biodegradability.(2)LA-I2-BOP-RGD nanorods with high drug loading rate and targeting photodynamic therapy were constructed by self-assembly of LA and photosensitizer molecules I2-BOP.In vitro experiments showed that the loading rate of photosensitizer can be as high as 97.84%,has a high efficiency of singlet oxygen generation,indicating that its special rod-like structure makes the photosensitizer molecules exit in a monodispersed state,which is beneficial to improve the photodynamic therapy effect;MTT experiment shows that the inhibition rate of HeLa cells was as high as 85%.The above research results show that using of LA amphiphilicity and drug molecules for self-assembly,with a simple preparation process,low toxicity,degradable,is a promising nano drug carrier.In the third chapter,the Cur-I2-BOP nanospheres with good stability and high drug loading rate(64.2%of Cur;22.9%of I2-BOP)were obtained by the self-assembly using the organic hydrophobic drug molecule Cur and the photosensitizer molecule I2-BOP.Under the microenv:ironment of the tumor,the drug molecules were released by low pH and used for cancer chemotherapy,while under light,I2-BOP can produce singlet oxygen for photodynamic therapy.The results from in vitro release experiments showed that the drug release was 72%in response to pH=5.0;MTT experiments showed that the inhibition rate of HeLa cells reached 75.2%within 24 hours.So the system combines chemotherapy and photodynamic therapy,which is a degradable drug carrier.