Synthesis Of Amphiphilic MRI Contrast Agent And Their Application As Potential Drug Delivery System

Magnetic resonance imaging(MRI)technology is one of the main means of detection for early diagnosis of cancer,but the contrast of medical magnetic contrast agents(CAs)is not enough to distinguish between disease and normal tissue.Recently,contrast agents with high contrast were constantly developed.Because of strong imaging signal,the T1 type contrast agents have attracted much attention.In addition,the realization of diagnosis and treatment integration has been a hot topic in drug delivery system.This paper aims to develop a novel amphiphilic T1-weighted MRI contrast agent whose aggregations show promising theranostic drug carriers applications.We synthesized Gd-DTPA-BA(n)with the length of hydrophobic chains of 12?14 and 16 and Gd-DTPA-Nn-n with the length of hydrophobic chains of 10 ? 12 ? 14 and 16 respectively.The intermediates and target products were confirmed by MS,1H NMR and IR.The surface tension test showed that Gd-DTPA-BA(12)had a high surface activity.As the carbon number of hydrophobic chain increased,the surface activity of Gd-DTPA-BA(n)decreased.And stable aggregations were not formed by Gd-DTPA-BA(n)in the solution.The Gd-DTPA-Nn-n had a high surface activity.The surface activity increased as the carbon number of hydrophobic chain the increased.And Gd-DTPA-N16-16 with low critical micelle concentration(cmc at the order of 10-6mN/m)showed good surface activity.Gd-DTPA-Nn-n demonstrated good relaxation performance.And the longitudinal relaxation efficiency(r1)increased from 11.20 to 16.83 mM-1s-1with the carbon number of hydrophobic chains increasing from 10 to 16.In vitro magnetic resonance imaging indicated the excellent imaging properties of Gd-DTPA-Nn-n.Therefore Gd-DTPA-Nn-n is a potential T1-weighted magnetic contrast agent.Dynamic light scattering(DLS)and transmission electron microscopy(TEM)measurements comfired the Gd-DTPA-Nn-n could form stable vesicles in PBS buffer solution.Furthermore,anti-tumor drug doxorubicin(DOX)was loaded into the vesicles of the Gd-DTPA-Nn-n with a high drug loading efficiency(DLE).And the DLE increased as the size of vesicles increased.In addition,the DLE of vesicles formed by Gd-DTPA-N16-16 was 68.23%,which was much higher than that of the reported drug carriers.The zeta potentials measruments indicated the good stability of the drug-loaded vesicles.The in vitro release of DOX-loaded Gd-DTPA-N16-16 vesicles showed the faster DOX release in the acidic environment.Therefore its in vitro release could be controlled by adjusting the pH.MTT cytotoxicity test showed that when the concentration of Gd-DTPA-N16-16 was lower than 250 ?g/m L,Gd-DTPA-N16-16 had no significant toxicity to MCF-7 cells and normal HL-7702 cells.Compared with free DOX,DOX-loaded Gd-DTPA-N16-16 vesicles showed higher anticancer activity.Gd-DTPA-N16-16 vesicles wrapped with lower concentrations of DOX could achieve therapeutic effect.The intracellularization of drug-loaded vesicles was observed by fluorescence confocal microscopy.Drug-loaded vesicles could pass through the MCF-7cell membrane into the cytoplasm.In short,Gd-DTPA-N16-16 vesicles demonstrated promising potential for theranostic applications.