| Gastric cancer is one of the most common malignancies in the digestive system.In the recent five years,gastric tumors have emerged as the second cause of incidence rate in China,and the gastric cancer-associated mortality is third.Owing to no obvious symptoms for early gastric cancer,once found,80% of the patients have reached late stage.Due to lack of treatment methods,effective tools for detection of and therapy for gastric cancer are desperately required for minimizing the morbidity and mortality rates.With the rapid development of nanotechnology,design of multifuctional nanoprobes has been attracted more attention in gastric cancer diagnosis,treatment and posttreatment monitoring.With unique physical and chemical properties,such as hypotoxicity,easy separation under external magnetic field,high saptial resolution and tomography and so on,Fe3O4 nanoparticle is widely used in biomedical fields,including solid phase separation,protein fixation,magnetic resonance imaging,drug delivery,gene delivery,nanosensors and magnetic fluid heat therapy.In the present work,a ultra-small and fluorescent/magnet-mediated nanoprobe(Fe3O4-PEG2k-FA@Ce6)with high-stability has been developed.This nanoprobe is composed of Fe3O4 NPs,folic acid(FA),amino difunctional polyethyleneglycol(NH2-PEG2k-NH2)and photosensitizer chlorin e6(Ce6).The superparamagnetic Fe3O4 NPs with carboxyl is synthesized on a large scale by a one-pot hydrothermal process and are stable in an aqueous environment for more than eight months.Compared with free Ce6,the Fe3O4-PEG2k-FA@Ce6 nanoprobes signifcantly enhance cellular uptake effeciency and promote the effectiveness of photodynamic therapy(PDT)with the assistance of633 nm laser irradiation.The inhibition rate of tumor is 69%.The unique nanoprobes show superior penetration and a retention time of more than six days in tumor with less accumulation in the liver,allowing highly effective tumor recognition and real-time monitoring.Additionally,there was little damage to healthy organs or tissues in abscence of laser irradiation.However,further extension of retention time of nanoprobes in the tumor region and reducing the accumulation of nanoprobes in the normal organs(for example,lung,liver and spleen)is crucial for high-efficiency photodynamic therapy of gastric cancer.Herein,we systematically report three ultra-small and highly stable nanoplatforms with Fe3O4 NPs diameters of 4,8 and 13 nm.Owing to the synergistic virtues of markedly active targeting and intrinsic small size effect,the Fe3O4@P-NPO/PEG-Glc@Ce6nanoprobes can effectively prolong their residence time in the tumor region and reduce accumulation in the normal organs.Meanwhile,benefitting from the small size effect,the synthesized Fe3O4@P-NPO/PEG-Glc@Ce6 nanoprobes exhibited excellent tumortargeting capability and photodynamic therapeutic efficacy by inhibiting the growth of tumors in mice under visible red light irradiation with a relatively lower power.Compared with free Ce6,the tumor inhibition rate of NP-13 nm nanoprobe is as much as 77%.Based on the small size effect,both NP-4 nm and NP-8 nm nanoprobes significantly improve the PDT efficiency in our strategy,which is as new building blocks for PDT of gastric tumor.The tumor inhibition rate of NP-4 nm and NP-8 nm is66% and 71%,respectively.Finally,Owing to their hypotoxicity,great spatial resolution and tomographic properties,Fe3O4 NPs is as one of the most promising materials for shape-dependent therapeutic agents for malignant tumor therapy under the magnetic resonance imaging guide.Conventional spherical Fe3O4 NPs is unable to effectively destroy cellular structure in therapy,thus it results in tumors with a high risk of drug resistance.Herein,we developed a flower-like targeted Fe3O4@Au-HPG-Glc nanoprobe that can enhance the efficiency of gastric cancer treatment under MRI.Under an alternating magnetic field(AMF),the flower-like Fe3O4@Au-HPG-Glc nanoprobes can rotate along the central axis of the core to destroy tumor cells by damaging the nucleus or cell membrane.The results showed that this nanostructure-dependent therapeutic agentbased strategy had remarkable efficacy for MRI-guided tumor therapy.Compared with the level of inhibition in a blank group,the inhibition of tumor growth in tumor-bearing mice was up to approximately 47.3% on the twelfth day of treatment.Different from other reported methods for gastric cancer therapy,our proposed AMF-dependent targeted gastric cancer therapy could potentially reduce drug resistance in gastric tumors. |
PDF Full Text Request