Basic Research Of Multifunctional Superparamagnetic Fe₃O₄ Nanoprobes For Targeted Therapy

In China,gastric cancer is already the second largest cancer.Most gastric cancers are adenocarcinomas,which have no obvious symptoms in the early stage and are easily ignored.At present,the three commonly used clinical methods of chemotherapy,radiotherapy and surgical resection have the problems of long treatment cycle,large side effects,weakened immune function and incomplete resection.In addition,it is still very challenging to solve the problems of tumor metastasis and drug resistance.Therefore,it is urgent to develop effective tools for the diagnosis and treatment of gastric cancer.With the development of nanotechnology,Fe₃O₄ nanoparticles have unique physical and chemical properties,such as low toxicity,easy surface functionalization and superparamagnetic properties,so magnetic nanoprobes based on Fe₃O₄nanoparticles have been widely used in the diagnosis,imaging,and treatment of malignant tumors.In this study,we prepared a novel superparamagnetic Fe₃O₄-PEG-G5-MMP2@Ce6 nanoprobe for dual-mode imaging and photodynamic therapy of gastric cancer.The nanoprobes consists of magnetic Fe₃O₄ nanoparticles,polyethylene glycol（PEG）,dendrimer PAMAM（G5）,matrix metalloproteinase 2（MMP2）and photosensitizer chlorin e6（Ce6）.The average diameters of the prepared Fe₃O₄nanoparticles and Fe₃O₄-PEG-G5-MMP2@Ce6 nanoprobes were 6.39±0.9 nm and 8.85±1.22 nm,respectively.The Ce6 loading of Fe₃O₄-PEG-G5-MMP2@Ce6 nanoprobes was about 19.73 wt%,and the saturation magnetization was 3.2 emu g-1.In vitro MTT assay and apoptosis experiments showed that the viability of MGC-803 cells incubated with Fe₃O₄-PEG-G5-MMP2@Ce6 nanoprobes for 12 h was only 38.17%and 37.1%under the 633 nm laser irradiation.Meanwhile,Fe₃O₄-PEG-G5-MMP2@Ce6 nanoprobes also exhibited good stability,biocompatibility and precise tumor targeting.At the same time,Fe₃O₄-PEG-G5-MMP2@Ce6 nanoprobes could be used for near-infrared（NIR）fluorescence imaging and T₂ weighted magnetic resonance imaging（MRI）of gastric cancer in vivo.The presence of the molecule MMP2 effectively enhanced the tumor targeting ability of the Fe₃O₄-PEG-G5-MMP2@Ce6 nanoprobes.Furthermore,under the irradiation of a 633 nm laser,Fe₃O₄-PEG-G5-MMP2@Ce6 nanoprobes could significantly inhibit tumor growth the tumor size increased 1.5times compared with the initial,and had no obvious side effect on other normal tissues and organs.