Bone Targeted Nanoparticles For Metastatic Bone Tumors Photothermal Therapy

ObjectiveMetastatic Bone Tumors have a high incidence as a fatal complications of cancer,which still currently lack effective clinical treatment.Common treatments include surgery,radiotherapy,chemotherapy,but all these therapies have defects.Surgical treatment has large trauma,easily to relapse;radiotherapy can increase the risk of malignant transformation;chemotherapy can lead toxic side effects that the patients are difficult to withstand the continued treatment.Therefore,it is very important to find a new idea for the treatment of metastatic bone tumor with bone targeting ability,low toxicity,less side effect and good treatment effect.Photothermal therapy is a new strategy for treatment for many types of tumors,and has many advantages over traditional methods.Near infrared light can penetrate biological tissue deeply into the tumor,and excite targeted nanoparticles to convert light energy into heat energy,improving tumor temperature accurately,which can reduce injury normal tissue,and kill tumor by local overheating.Therefore,the application of photothermal therapy in the treatment of metastatic bone tumors has a good clinical prospect.At present,there are few studies on photothermal therapy for metastatic bone tumors.The development of nanomaterials with bone targeting ability is the key to the successful application of photothermal therapy for the treatment of metastatic bone tumors.It has been proved that photothermal nanomaterials can be used in photothermal therapy of various metastatic tumors.But the studies of photothermal therapy treating metastatic bone tumor are less.The existing thermal materials have poor bone targeted ability,poor light-heat properties,bad biocompatibility and that chronic toxicity caused by large volume,limiting its application of photothermal therapy in metastatic bone tumors.So the suitable design for the new nano materials of metastatic bone tumor photothermal therapy,which have bone targeting ability,heat resistance,biological safety,easy removal from the body and other characteristics,is an important basis for the metastatic bone tumors photothermal therapy.In this study,a new type of ultra-small phytic acid-platinum nanomaterial was prepared by using phytic acid as the target material.The ability of phytic acid to chelate calcium ion is strong,and phytic acid has the potential ability to target bone tumor,low toxicity,and anti-tumor activity,which can inhibit the growth of cancer cells to a certain extent.Platinum nanoparticles have high efficiency of light and heat conversion,with goog biological safety.The size of the phytic acid-platinum nanomaterials is within 5 nm,which can be quickly removed through the kidney,reducing the retention of nanoparticles in body.Through the research of this new type of phytic acid-platinum nanomaterial,this paper has discovered the synthesis,bone targeting ability,thermal properties,biological safety features,and treatment effect of the nanomaterial for metastatic bone tumor photothermal therapy effect,providing a new idea for the development of new technology for the metastatic bone tumors photothermal therapy.Methods(1)Preparation and characterization of phytic acid platinum nanoparticles: Platinum nanoparticles were synthesized by using platinum chloride acid,Sodium Citrate and phytic acid.The size and morphology were observed by transmission electron microscopy;(2)Chelating ability and photo thermal efficiency of phytic acid platinum nanoparticles: the photothermal effect of phytic acid platinum nanoparticles.Application of artificial bone(hydroxyapatite)adsorption experiments to observe the chelating calcium ion ability of phytic acid platinum nanoparticles.(3)Cytotoxicity of phytic acid platinum nanoparticles: PC-9 cells were selected and the cytotoxicity of nanoparticles was observed by MTT method.(4)The treatment effect of metastatic bone tumor with phytic acid platinum nanoparticles: to establish a mouse model of metastatic bone tumor of lung cancer in nude mice,and to observe the effect of the photothermal treatment by near infrared light and the ability of bone tumor targeting.Results(1)We succeed to synthesize phytic acid platinum nanoparticles,and the platinum particles are on the surface of IP6.We find that these nanoparticles have good stability.All nanoparticles are in 2-3 nm,with similar form.(2)The results show that the phytic acid platinum nanoparticles have good absorption effect at 808 nm,and the thermal effect is good and effective.In the experiment of in vitro adsorption,we can find that the adsorption capacity of the experimental group is high and the adsorption capacity is strong.(3)The biocompatibility of phytic acid platinum particles was concentration dependent,and no obvious side effects were found in vitro.(4)The phytic acid platinum nanoparticles shows good in vivo bone tumor targeting ability in the nude mice model with metastatic bone tumor,and has good tumor inhibition,good biological safety,which indeed has the therapeutic effect on metastatic bone tumor under photo-thermal treatmentConclusionsIn this study,a new type of ultra small platinum nanomaterials was well prepared by using natural plant composition as the template.The material has the characteristics of small size and stable dispersion.It has several advantages as good bone targeting properties in vivo and in vitro and good biocompatibility without obvious side effects,good effects in photothermal therapy for metastatic bone tumor.The novel phytic acid platinum nanomaterials provide a new perspective for photothermal therapy of metastatic bone tumors.