Research Of The Application Of Novel Nanocomposites In Tumor Targeted Therapy

Research Background&PurposeWith the deteriorating environment and people’s poor lifestyles,the incidence of malignant tumors is still on the rise.According to the latest report of the World Health Organization in February 2018,cancer is the leading cause of death worldwide.It is estimated that more than 20 million new cases of cancer will occur in the world by 2020,while the number of deaths will reach 12 million.Because of its high incidence and fatality rate,malignant tumors is now seriously endangering the health of all human beings.Tumors also resulted to enormous and countless global costs.Chemotherapy,as one of the most commonly used methods for the treatment of malignant tumors,has made some achievement in the field of cancer treatment.And chemotherapy is now one of the major way to treat tumor.However,due to the toxicity of chemotherapeutic drugs,the toxic drugs distribute throughout the whole body after injection,which leading to huge damage of normal tissues and organs.What’s more,some patients might not be able to live with the toxicity and finally die.These shortcomings have greatly affected the drug’s curative effect.Therefore,targeted drug delivery is the key to improve this.In addition to chemotherapy,photodynamic therapy,as an emerging safe and effective therapy,is attracting increasing attention.However,photodynamic therapy-related photosensitizers are often with low solubility,extremely small nano-diameter,thus resulting to quick excretion,which definitely limited its application.Therefore,exploring novel photosensitizers with targeted ability is current research focus.Specifically,targeted drug delivery system improves the recruitments of chemotherapeutic drugs in the tumor area,enhances the drug efficacy and reduces systemic side effects;Targeted modification of new photosensitizers unlocks the limitation of photodynamic therapy for tumors which means a lot.MethodIn the present study,we first constructed a FA-targeted nanoscale graphene oxide（n GO）with Fe₃O₄ through hydrothermal method（FA-Fe₃O₄@n GO）,which is a novel folate-targeted graphene magnetic nanocomposite drug delivery system based on n GO,then DOX was loaded throughπ-πeffect,which turns out to be FA-Fe₃O₄@n GO-DOX nanocomposites.Followed by the evaluation of the apparent morphology,particle size and distribution,Zeta potential,drug loading and release,biocompatibility,targeting specificity and killing efficacy for bioavailability of the drug-loaded system.To further explore the potential value of photodynamic therapy for tumors,we synthesized superparamagnetic nanocomposites with Fe₃O₄ nanoparticles and black phosphorous by hydrothermal method,which will exhibit good photodynamic and photothermal effects theoretically.After conjugated streptavidin（SA）via polyethylene glycol（PEG）,a well-established targeted black phosphorous magnetic nanocomposite（SA-Fe₃O₄@BP）system is build.Various kinds of biotin-labeled tumor specific antibodies can bind with streptavidin conjugated to black phosphorus composites（Ab-SA-Fe₃O₄@BP）.In this experiment,a biotin labeled anti-HLA class I A11 antibody was used to construct a targeted phosphorous magnetic nanocomposite system to targeting human tumors.After comprehensive evaluation of the stability,apparent morphology,optical properties,biocompatibility,targeting recognition ability and killing properties of these nanocomposites,we find that the safety,effectiveness,smart and novel black phosphorous nanocomposites laid a foundation for future targeted photodynamic therapy of tumors.ResultsThe results showed that the biocompatibility of both FA-Fe₃O₄@n GO-DOX and Ab-SA-Fe₃O₄@BP nanocomposites are good,and both of them have the ability of targeting to tumors.The FA-Fe₃O₄@n GO-DOX can easily binding with folate receptor,which is highly expressed on the surface of tumor cells,and the latter can identify tumors by specific tumor markers（such as VEGFR2,etc.）;both of them are combined with Fe₃O₄superparamagnetic nanoparticles,which can be used for MRI contrast agents for tracking and tumor diagnosis;both can be used for killing tumors,the former is through the loaded chemotherapeutic drugs while the latter is through photodynamic therapy.The advantage of FA-Fe₃O₄@n GO-DOX is based on tailored graphene oxide drug delivery system with improved stability,and achieves targeted drug delivery and controlled drug release.Different chemotherapeutic drugs can be loaded to the drug delivery system to treat the majority of tumors theoretically;Ab-SA-Fe₃O₄@BP nanocomposites are based on the two-dimensional black phosphorous.The conjugated streptavidin on the surface enabled all the biotin labeled antibodies（tumor specific or not）to binding with the nanocomposites,making them to be a universal targeting system for different diseases.By using the photodynamic as well as photothermal effects,the nanocomposites themselves can achieve a variety of different tumors targeted killing.ConclusionIn this study,we prepared two different targeted nanocomposites which can be used for tumor targeted therapy.The novel FA-Fe₃O₄@n GO nanocarrier system with excellent biocompatibility is more conducive to tumor targeting chemotherapy.The novel Ab-SA-Fe₃O₄@BP nanocomposites showed good biosafety and tumor-targeted killing effect,which bringed new ideas for the photodynamic therapy of tumors.