Magneto-Fluorescent Nanoprobes Construction And Application In The Gastric Cancer Theranostics

Objectives:This study aimed to prepare two types of multifunctional nanoprobes for gastric cancer targeting and dual-mode MR/FL imaging guided chemo-phodynamic or chemo-phothermal therapy.Methods:1.Preparation of Gd-DTPA and folic acid-conjugated BSA(^GdDF-BSA) and Gd-DTPA,folate and Ce6-conjugated BSA(^GdDBCF complex),and measure the T1 relaxivity of functionalized BSA.2.Oleylamine embedded and DOX encapsulated hollow structures are prepared by double-emulsion method.Via electrostatic adsorption,the nanocapsules are further assebled by hollow structures and ^GdDBCF complex,the EE,DL and cumulative release of DOX and Ce6 are then calculated.The morphology and charge of the nanocapsules are characterized by TEM,DLS and Zeta potential.3.Via co-solvent and ultrasound homogenization,IR-780 and cisplatin are encapsulated by ^GdDF-BSA nanocages to form protein-based complexes.Via chelation of gadolinium,protein-based complexes are self-assembled into nanoprobes.EE and DL of IR-780 and cisplatin are calculated,and measure their T1 relaxivity.4.The efficacy of photodamage and specific targeting of nanoprodes for MGC-803 cells are observed by fluorescence microscope.In vitro cellular uptake and endocytosis experiments and the cytotoxicity experiments of the nanoprobes are tested.A fluorescence imager and MR system are used to track the tumor targeting of nanoprobes,and furhter assess the in vivo therapeutic effects.Results:1.The size of nanocapsules and hollow structures were 154.21 nm and131.78 nm respectively,combined with the results of FT-IR and UV-vis spectra,it is confirmed that the nanocapsules were assembled from the hollow structures and ^GdDBCF complex.The results of Zeta potential and cumulative release showed that the nanocapsules had a charge-switchable property.2.TEM images showed that the protein-based complexes were assembled into nanoparticles with a diameter of 50 nm via chelation of gadolinium.3.Its T1 relaxation increased to 26.391 s^-1/mM,which was higher than ^GdDF-BSA(15.233 s^-1/mM)and 6.8 times larger times than Gd-DTPA.4.In vitro experiments showed that nanocapsules had a specific targeting and synergistic effects on MGC-803 cells,and also presented multistage responsive behaviors.5.In vivo MR/FL imaging of the nanoprobes showed that their selective accumulation and long retention time at the tumor site,and in vivo therapeutic experiments further showed that the therapeutic effect of the nanoprobes were better than a single one.Conclusions:1.Nanocapsules have a charge-switchable property and exhibit multistage responsive behaviors.2.Due to the incorporation of gadolinium,the relaxation efficiency of protein-based nanoprobes get obvious increase.3.The as-prepared nanoprobes both present a specific targeting and combined therapeutic effects on gastric cancer MGC-803 cells.And both the two kinds of nanoprobes exhibit MR/FL contrast imaging and present effective tumor inhibition and tumor ablation.