动力学效应诱导的近红外光响应温和光热治疗

Dynamic Effect Induced Near-infrared Light Responsive Mild Photothermal Therapy

癌症是世界上高致死率的疾病之一,传统治疗方法如化疗、放疗和手术等由于其局限性而常常使疗效不尽如人意。光热疗法(Photothermal therapy,PTT)是基于光热治疗剂的光热转换效应,将近红外光能量转换为热能并杀死癌细胞。然而,PTT消融肿瘤所需的温度较高,通常会引起周围正常组织/器官的损伤。采用较低治疗温度(38~43℃)的温和光热治疗(Mild photothermal therapy,mPTT)对于推动PTT进入肿瘤临床治疗具有重要意义。但是,即便小幅度的温度升高也会使癌细胞处于热应激状态并使热休克蛋白(Heat shock pro⁃teins,HSPs)表达上调,影响mPTT对癌细胞的杀伤效果。为了改善mPTT的治疗效果,本研究以树枝状介孔硅包覆稀土荧光纳米晶的纳米复合材料(DCNP@DMSN)作为基质材料,在其表面上修饰MnFe2O4纳米酶并在孔道内装载吲哚菁绿(ICG),设计了一种近红外荧光成像介导和动力学效应诱导的近红外光(NIR)响应mPTT协同治疗体系。该体系呈现出肿瘤微环境响应的化学动力学效应和近红外光激发的光动力学效应,产生的活性氧物质及脂质过氧化物可下调低温光热处理产生的热应激性HSP70的表达,实现动力学效应诱导的mPTT,在4T1乳腺癌中显示出良好的抗肿瘤性能。同时,该平台具备近红外二区荧光成像功能,可实现对活体肿瘤的定位。这对开发多功能诊疗一体化纳米平台,实现治疗过程的可视化、个体化以及精准化,改善肿瘤治疗效果具有重要意义。

Cancer is one of the most lethal diseases globally.Traditional treatment modalities like chemotherapy,radiotherapy,and surgery often fall short due to their limitations.Photothermal therapy(PTT),which utilizes the photothermal conversion effect of photothermal therapy agents(PTAs)to convert near-infrared energy into heat for cancer cell destruction,typically requires high temperatures that can damage adjacent normal tissues/organs.Mild photothermal therapy(mPTT)with a lower treatment temperature range(38-43℃)is crucial for advancing PTT in tumor clinical treatment.However,even a minor temperature increase can induce heat stress in cancer cells and up⁃regulate the expression of heat shock proteins(HSPs),affecting mPTT’s efficacy.To enhance mPTT’s therapeutic effect,in this study,a near-infrared(NIR)fluorescence imaging-mediated and kinetic effect-induced NIR-responsive mPTT synergistic therapeutic system was designed using dendritic mesoporous silica-coated rare earth fluorescent nanocrystal nanocomposites(DCNP@DMSN)as the matrix material,modified with MnFe2O4 nano-enzymes on the surface and loaded with indocyanine green(ICG)in the pore channels.DDMFI displays tumor microenvironment-re⁃sponsive chemical kinetic effects and NIR-activated photodynamic effects.The generated reactive oxygen species and lipid peroxides can downregulate the expression of heat stress-induced HSP70 from low-temperature photother⁃mal treatment,enabling kinetic effect-induced mPTT.In a 4T1 breast cancer model,it shows promising anti-tumor performance.Additionally,the platform has near-infrared second region fluorescence imaging functionality for in vivo tumor localization.Collectively,this approach holds great significance for the development of multifunctional integrated nano-platforms.