MRI/PAI For Tumor Microvascular Permeability Assessment And Photothermal Therapy Reactivity Monitoring

In the treatment of cancer,the development of nanotechnology offers the possibility of specific heat transfer.Photothermal therapy(PTT)has been widely studied due to its selective tumor elimination and its small damage to surrounding normal tissues.Some nanomedicines have also entered clinical trials.However,different types of tumors or different stages of the same tumor have very different PTT responses mediated by the same nanoparticles(NPs),resulting in completely different therapeutic outcomes.In PTT,the enhanced permeability and retention(EPR)effect of nanomaterials largely determines the intratumoral accumulation of nanomaterials and the photothermal reactivity of tumors,while the EPR effect is closely associated with the microvascular characteristics of tumors.Such as blood flow,perfusion and vascular permeability.Therefore,to study the relationship between the tumor microvascular characteristics and the EPR effect of nanoparticles and the corresponding tumor photothermal response,and to study whether the regulation of tumor microvascular characteristics can change the EPR effect of nanomaterials will be more conducive to the guidance of nano drug selection and development of different treatment plan,further promoting the clinical transformation of nanomedicine.In addition,the development of multiple imaging technologies has facilitated the visualization of the in vivo delivery,distribution,metabolism of nanomaterials,and enables accurately and comprehensively assessing the photothermal treatment results of tumor tissue,greatly broadening the in-depth application of photothermotherapy.Therefore,in this study,we aimed to combine noninvasive magnetic resonance imaging(MRI)and photoacoustic imaging(PAI)to study the correlation between tumor vascular permeability and nanoparticle EPR effects and the corresponding photothermal response of tumors.In this experiment,we first established a model of hypervascular permeability tumor(4T1 mouse breast tumor)and a model of hypovascular permeability tumor(HUH-7 human hepatoma).The dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)method was used to evaluate and confirm the vascular permeability of both tumors.Later,we synthesized a nanomaterial with good photoacoustic imaging and photothermal conversion efficiency,namely PEGylated tungsten disulfide(WS2-PEG)nanosheets.After a period of tail vein injection of WS2-PEG in experimental mice,photoacoustic imaging(PAI)was used to study the accumulation of the nanoplatelets in both tumor tissues.After the maximum amount of tumor tissue was accumulated,the tumor tissue was irradiated with 808 nm laser light.During the lighting process,a series of T1-weighted sequences were acquired,and the internal temperature of the tumor tissues in the light process was changed in real time according to the proton resonance spectrum(RPF)magnetic resonance temperature imaging method.After photothermotherapy,T2-weighted magnetic resonance imaging(T2W-MRI)was used to monitor tumor size changes,and diffusion-weighted magnetic resonance imaging(DW-MRI)was used to monitor tumor cell necrosis to evaluate the efficacy of photothermal therapy.Our results suggest that WS2-PEG has a higher accumulation in high vascular permeability tumors(HPT)than in low vascular permeability tumors(LPT).Under the same light conditions,HPT can reach higher temperature than LPT.For photothermotherapy efficacy monitoring,HPT photothermal therapy is superior to LPT.In conclusion,through this experimental study,we have designed a systematic and non-invasive method for assessing the relationship between tumor vascular permeability and EPR effects of nanomaterials and the corresponding efficacy of photothermal therapy.The combination of MRI and PAI can be used for tumor microvascular permeability assessment and photothermal therapy reactivity monitoring studies,and is expected to guide the future clinical transformation of PTT.