| Cancer is an increasingly serious disease for humans.The current treatment of cancer involves different traditional drug chemotherapy and single-targeted drug treatment,but the lack of or limited targeting property,leading to more side effects and poor treatment effect and brings to the patient a lot of pain.In order to reduce the adverse effects caused by lack of targeting and enhance the drug targeting property to improve the bioavailability of drugs and,we constructed a hyaluronic acid receptor(HA)-RGD peptide(RGD)-chlorambucil(CLB)-quantum dots(QDs)targeting drug delivery system with dual-targeting receptor.The current drug delivery system establishes the cross-linking of a non-targeting nitrogen mustard drug chlorambucil with dual-targeting receptor HA-RGD,in order to direct the drug selectivity to the tumor site or cells and increase the drug concentration at the tumor site,aiming to enhance the targeting property and improve the drug therapy effect.To prepare HA-RGD-CLB-QDs targeting delivery system,we deacetylated hyaluronic acid and removed the acetyl group from the chain catalyzed by co-catalysts of anhydrous hydrazine and hydrazine hydrate to release the active amino groups,enhancing the activity of hyaluronic acid binding sites.Then,we chemically cross-linked the anti-tumor drug chlorambucil and deacetylated hyaluronic acid in a neutral environment under an amide catalyst to produce single-targeted HA-CLB.Because of the synergistic targeting drug enhancement based on HA-RGD dual receptor,we used RGD through bridged methacrylamide(DMAPMA)under alkaline conditions by bonding HA-CLB with the addition reaction of olefins with click mercapto to prepare the HA-RGD-CLB with dual-mediated function.In order to achieve the in vivo imaging of the drug,we used mercaptopropionic acid as the stabilizer to prepare a stronger fluorescence and stability CdTe/CdS/ZnS nuclear/shell/shell quantum dots and HA-RGD-CLB crosslinked under alkaline conditions.And then the HA-RGD-CLB-QDs drug delivery system with multiple targeting and tracer function was prepared and the in vitro drug delivery study was carried out on the targeted drug delivery system.In order to further evaluate the HA-RGD-CLB-QDs targeting drug delivery system,the in vitro cytotoxicity,receptor competition inhibition and cell uptake of the targeted drug delivery system were investigated.We characterized the the HA-RGD-CLB-QDs targeting delivery system for nuclear magnetic spectrum(~1H NMR),Fourier transform infrared(FT-IR),transmission electron microscopy(TEM),dynamic light scattering particle size(DLS),X-ray photoelectron spectroscopy(XPS)and UV-FS spectroscopy(UV-FS).The results show that the compound is fully synthesized and the compound has good fluorescence effect and dispersibility,and the particle size is about 70 nm.HA-RGD-CLB-QDs drug release results show that the system displayed a good drug release of pH=5.5 environment and the drug cumulative release rate was 61%in 48hours,while at pH=7.4 environment the release of drug is only 12%,indicating that the drug delivery system has pH sensitivity and enzyme sensitivity.In addition,in vitro cell experiments results showed that HA-RGD-CLB-QDs targeting drug delivery system significantly increased the uptake of cancer cells compared with single targeting drug delivery system,increased the concentration of drugs in the tumor,had better anti-tumor effect and low toxicity to normal cells.Therefore,the targeted drug delivery system has a broad application prospect in the treatment of cancer. |
