| The multifunctional nano-theranostic agent can not only afford the information of accurate location of the tumor but also perform local treatment and monitor the treatment effect in real-time.It has broad application prospects in the field of cancer diagnosis and treatment.Multimodal imaging can provide more accurate and rich information by making up the inherent limitations of single imaging mode,accurately analyze the location of tumors in the body,guide treatment,monitor treatment results,and analyze prognosis.However,according to previous reports,it is difficult to completely remove the tumors by single therapy.In contrast,synergistic therapy can overcome the shortcomings of single treatment and obtain better treatment effect.Therefore,the development of versatile nano-platforms has become a current research hotspot.Herein,a multifunctional nano-theranostic agent Bi2S3-Mn O2@BSA-Ce6(BMBC)was successfully prepared for photothermal/photodynamic synergistic therapy of tumors under the guidance of infrared thermal(IRT)/MR/CT imaging.The tumor microenvironment has the characteristics of weakly acidic,hypoxia,and H2O2 overexpression.According to these characteristics,Bi2S3-Mn O2@BSA-Ce6 NPs were designed for T1-weighted MR/CT/IRT three-modality imaging-mediated photothermal/photodynamic synergistic therapy.The design principles of this nanoparticle are as follows:Mn O2 can respond to the tumor microenvironment to catalyze H2O2 to produce O2,which can not only alleviate the hypoxic environment but also improve the effect of photodynamic therapy.Mn2+produced by the reaction of Mn O2 with H+can achieve T1-weighted magnetic resonance imaging.Bi exhibits the excellent performance of IRT imaging and achieves photothermal therapy.At the same time,Bi has good X-ray attenuation performance and can be used as a CT contrast agent for CT imaging.Based on this,Ce6 was covalently linked to bovine serum albumin(BSA)through amidation reaction to prepare BSA-Ce6 as a template,and then multifunctional nano-theranostic Bi2S3-Mn O2@BSA-Ce6 was prepared under weakly alkaline conditions by biomineralization.These BMBC nanoparticles had a spherical morphology with an average particle size of 17.6±4.6 nm,and had a good dispersion and physiological stability.This agent possessed the outstanding performance of photothermal conversion(?=45.80%)under 808 nm laser radiation and generated 1O2under 650 nm laser irradiation.Due to the strong X-ray attenuation performance of element Bi and the highly effective magnetic moment of Mn2+,this agent exhibited favorable performance of X-ray computed tomography(CT)imaging(35.60 HU·m L·mg-1)and magnetic resonance(MR)imaging(r1=5.22 m M-1·s-1)in vitro.In addition,these agents exhibited good biocompatibility in the MTT and Calcein-AM/PI staining experiments.After a high concentration of 800 ppm Bi2S3-Mn O2@BSA-Ce6 was co-cultured with Hela cells for 48 hours,the cell survival rate was still higher than 90.00%,indicating that the agent was almost non-toxic and exhibited good biocompatibility.The cells co-cultured with the nano-theranostic agents were irradiated with 808 nm and 650 nm lasers,and the cell survival rate was only 10.61%,demonstrating the excellent effect of intracellular synergistic therapy.The above experimental results indicated that the agent Bi2S3-Mn O2@BSA-Ce6 not only had T1-weighted MR/CT/IRT three-modal imaging capabilities but also had excellent performance in photothermal/photodynamic synergistic therapy,exhibiting a promising potential in the early diagnosis and treatment of tumors. |
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