Sythesis And Anti-tumor Porperties Of Several Photothermal Nanomaterials

Cancer is one of diseases that threatens human health tremendously.However,traditional therapies including radiotherapy,chemotherapy,and surgery not only fail to achieve the satisfactory therapeutic effect but also cause serious side-effect.Therefore,exploring the new cures for cancer is a hot topic nowadays.The development of nanotechnology has brought promising prospects for the treatment of cancer.Novel therapies based on nanomaterials can kill tumor cells with high efficacy.Among them,photothermal therapy（PTT）has caught worldwide attention due to its fascinating advantages,including minimal invasiveness,high spatial controllability and less harmful to normal tissues.In addition,integrating imaging and therapy into one nanoplatform could achieve imaging guided-therapy.However,the potential toxicity of nanomaterials caused by their long-term retention in vivo prevents them from further application.Therefore,it is significant to synthesize nanomaterials with high treatment efficiency and good biosafety.To this end,we conducted the following research work in this paper:1.Nowdays,the majority of photothermal agents（PTAs）triggered by the lights in the first biowindow（NIR-Ⅰ,750-1000 nm）for PTT.Compared with NIR-Ⅰ light,lights in the second biowindow（NIR-Ⅱ,1000-1350 nm）with higher MPE,deeper tissue penetration depth,and lower light scattering,are more suitable for PTT.Therefore,it is urgent to design novel PTAs with strong absorption and high photothermal conversion efficiency（PCE）in the second biowindow.In this work,we synthesized carambola-like Bi₂Te₃ superstructures as nanotheranostic agents for CT imaging-guided PTT in the second biowindow.Benefiting from their carambola-like superstructures,Bi₂Te₃@PEG showed enhanced absorption in NIR-Ⅱregion,resulting in high PCE（55.3%for 1064 nm）.Furthermore,Bi₂Te₃@PEG exhibited high contrast efficacy as CT contrasts in vitro and in vivo owing to the high X-ray attenuation coefficient of Bi.The tumors have been effectively eliminated after 14 d treatment,demonstrating the good treatment effect of PTT in the NIR Ⅱ biowindow.This work provides a new insight for design highly effective PATs with good photothermal performance through the structure regulation.2.Integrating T₁/T₂-weighted dual-mode magnetic resonance imaging（MRI）functions into one nanoplatform is a promising strategy for highly efficient cancer diagnosis.So far,many efforts have been devoted to construct nanocomposites as contrasts for T₁/T₂-weighted bimodal MRI.However,the defects of nanocomposites,including the complicated synthesis process and instability,prevent them from further clinical application.Therefore,it is highly desired to explore single nanomaterial as contrast for Ti/T₂-weighted bimodal MRI.Herein,we synthesized MnCo₂O₄ nanodots as nanotheranostic agents for T₁/T₂-weighted bimodal MRI-guided PTT.Due to the intrinsic magnetic property of Mn and Co,MnCo₂O₄@PAA can work as contrast agents for T₁/T₂-weighted bimodal MRI,providing more comprehensive information for diagnosis.Furthermore,benefiting from ultrasmall size and excellent absorption in the NIR region,MnCo₂O₄@PAA can penetrate deeply into tumor,and effectively ablate tumor in vitro and in vivo.What is more,MnCo₂O₄@PAA can almost be completely cleared from mice at 7 d postinjection,implying their negligible long-term toxicity.All these findings demonstrate that the ultrasmall MnCo₂O₄@PAA nanodots with good MRI ability,excellent treatment efficacy of PTT,as well as rapidly systemic clearance ability have great potential in further clinical application.3.The nonspecific targeting of chemotherapeutic drugs always causes severe damage to normal tissues.Therefore,it is of great significance to explore nanoplatforms that not only can act as carriers of chemotherapeutic drugs but also can release the payload responding to the tumor microenvironment（TEM）.Herein,we synthesized a novel nanocomposite(CaCO3@DHA@Fe³⁺-TA@PEG,designated as CDFP NPs)for synergistic cancer therapy.Specifically,CDFP NPs enriched at the tumor site can kill the tumor cells by the photothermal effect with the irradiation of 808 nm.Interestingly,CDFP NPs show pH-sensitive dissociation feature,which allows to rapid release of TA,Fe³⁺,DHA,and Ca²⁺ in the acidic TEM.And TA will reduce Fe³⁺to Fe²⁺,followed by interacting with DHA to produce reactive oxide species（ROS）.Furthermore,intracellular overloaded Ca²⁺ leads to the mitochondrial dysfunction under oxidative stress,which will further induce tumor cell apoptosis.CDFP NPs integrated with PTT,ROS,and Ca²⁺overloading show remarkable anticancer effect in vitro and in vivo.This work achieves the pH-sensitive DHA release and self-supply of ferrous ion,offering great potential for further clinical application of DHA.