Targeting Multifunctional Magnetic Nanoparticles For Tumor Imaging And Therapy

Magnetic nanoparticles have been used widely in biomedicine and therapy.Magnetic nanoclusters(MNCs)composed of numerous of ultrasmall superparamagnetic iron oxides nanoparticles(USPIOs)can maintain the superparamagnetism and increase the transverse relaxivity with the increasing sizes,which provides great potential application in MRI.MNCs,which act as the magnetic core of the multifunctional nanoparticles,can combine with optical imaging to form a dual-modality imaging agent.MNCs can be also coated with mesoporous silica shell loading with therapy agents to form a drug delivery system(DDS)for tumor.In this paper,we would develop two multifunctional nanoparticles containing MNCs for targeting tumor imaging and therapy.We synthesized MNCs(size of 100 nm)coated with a fluorescent silica shell doped with Ru(?),which termed as FMNPs.After PEGylation,RGD peptides were conjugated to the surface of FMNPs for targeting imaging of breast cancer.We select the human breast cancer cell line MDA-MB-231 in which the integrin ?v?3 was overexpressed for animal model.The biocompatibility of RGD-FMNPs was evaluated both in vitro and in vivo.The relaxation time of T2 in MRI of RGD-FMNPs was three times as that of FMNPs(12.867±0.451 ms vs.4.833±0.513 ms,p<0.05).There was no obvious toxicity observed both in vitro and in vivo which indicated good biocompatibility of RGD-FMNPs.Conclusion:RGD did increase the uptake of RGD-FMNPs by breast cancer cells.We developed a drug delivery system composed of a MNCs core and a mesoporous silica shell(MMNPs).The MNCs were synthesized through a modified hydrothermal reaction and the average size was about 20 nm.After modified with PEG and RGD peptides,which were used as the targeting probe,the MMNPs were loaded with gemcitabine and used for targeting therapy of pancreatic cancer.We chose three human pancreatic cancer cell lines(BXPC-3,PANC-1,CFPAC-1)in which the expressions of integrin ?v?3 were different to evaluate the therapeutic effects of RGD-MMNPs loaded with gemcitabine.Conclusion:BXPC-3 could uptake more RGD-MMNPs and are more sensitive to the therapy.RGD could enhance the cellular uptake of RGD-MMNPs in pancreatic cancer cells.