The Preparation Of Functional Nanoparticles Based On PGMA And Its Application In The Aspect Of Medicine

Cancer has become a serious threat to human life. In the world, deaths caused bycancer have reached millions of people each year and also continue to grow at analarming rate. Therefore, early diagnosis and effective treatment of cancer havebecome a hot research. Quantum dots have the adjustable fluorescent, broad emissionspectrum, narrow excitation spectrum and long life, etc. It has the potential for usingin the diagnosis of tumors. But quantum dots obtained by traditional methods areinsoluble in the water, easy to accumulation, poor stability and have othershortcomings. The most common cancer treatment is chemotherapy, conventionalchemotherapy administered with low efficiency, has side effects, can lead to multidrugresistance and has other shortcomings. In order to make the quantum dots and theanticancer drug can be better applied to cancer diagnosis and treatment, differentmodifications and effective improvement are needed. In this article, PGMA was usedto prepare cancer diagnostic reagents and therapeutic agents with different functionsand features.First, we use the ATRP polymerization process for preparing homopolymerPGMA with low molecular weight and narrow distribution. By ring-opening reactionand the use of EDA, comb polymers PGMA-g-EDA is formed and have a largenumber of amino. The polymer has good hydrophilicity, can modify oil-solublequantum dot by ligand exchange to form water-soluble quantum dot. UV andfluorescence spectra showed that the structure of the quantum dots was not destroyed,maintain the original excellent optical properties. DLS and TEM indicated quantumdots have a smaller particle size and good dispersibility in aqueous solution. Finally,the study on the stability of quantum dots showed that the QDs have good atability.Secondly, His was grafted onto the polymer PGMA-g-EDA and the pH-sensitiveamphiphilic polymer PGMA-g-EDA-g-His was prepared. Under neutral or alkalineconditions, imidazole was deprotonated and histidine fragments become hydrophobic,micelles were formed by polymer PGMA-g-EDA-g-His. However, under acidic conditions, imidazole was protonated. Histidine fragments become hydrophilic.Micelles were dissociated. In this paper, polymer with different grafting amount ofHis was prepared to verify the impact of the grafting level on the pH sensitivity,particle size, morphology, the critical micelle concentration. FinallyPGMA-g-EDA-g-His2.0polymer with the best grafting rate was used to coat drug. Invitro drug release studies and cells experiments show thatPGMA-g-EDA-g-His2.0@DOX has the different drug release behavior at different pH,and a high concentration of the drug will be occurred in the tumor cells. As a result ofthis, the tumor cells can be effective destructed and the growth will be inhibited.Thirdly, a pH-sensitive theranostics was designed based on the polymerPGMA-g-EDA-g-PEG. First, PEG was grafted onto the polymer PGMA-g-EDA tofurther enhance its hydrophilicity. Secondly, PGMA-g-EDA-g-PEG was used tomodify quantum dots by ligand exchange to enhance hydrophilicity. Finally,anticancer drug was connected onto the surface of quantum dot nanoparticles throughthe pH-sensitive imine bond to yield the final diagnosis and treatment agent. UV andfluorescence tests showed that after modification, the structure of the quantum dot andDOX wasn’t destroyed, and retained the original optical properties and therapeuticeffect. In vitro drug release studies showed that the system was pH sensitive. Themajority of drug was released at the pH of5.0. While at pH7.4, the micelle was stable,and drug was hardly released.Finally, the pH-sensitive theranostics was further improved and functioned. Inhere, folic acid was chose as the target molecule, a pH-sensitive and targetedtharanostics was prepared by the use of PGMA-g-EDA-g-PEG-g-FA, QDs and DOX.Cell experiments showed that after connecting the target molecule, quantum dots anddrug can easily enter the cell, resulting in a high concentration of drug in the cells, canfurther enhance the effects of tumor’s diagnosis and treatment.In a summary, the cancer diagnostic and therapeutic agents with differentcharacteristics and functions were successfully prepared on the base of PGMA. Theseagents have broad application prospects in the fields of diagnosis and treatment ofcancer.