Nanoparticles With Strong Absorbance In NIR-? Window For In Vivo Photothermal Therapy And Photoacoustic Imaging

In recent years,near-infrared(NIR)light-induced photothermal therapy(PTT)has attracted much attentions.Photothermal therapy is a non-invasive treatment of cancer by converting the absorbed light energy into thermal energy around the tumor tissue through photothermal agents to produce photothermal toxicity so as to kill the tumor cells.Due to the spatiotemporal controllability of the light source,photothermal therapy can effectively reduce the side effects during clinical chemotherapy and achieve an accurate treatment of tumor.Therefore,the photothermal therapy is a very promising tumor treatment method in clinic.The tissue penetration ability of infrared light with wavelength between 650 nm and 1350 nm is obviously stronger than that of ultraviolet or visible light.In the NIR region,tissue penetration ability of the second biological near-infrared window(1000~1350 nm)is recognized to be stronger than that of the first window(650~950 nm).However,NIR light absorbers in the second NIR region(NIR?)have been scant even though various NIR light absorbers in the first NIR region(NIR-I)have been widely explored.Therefore,the development of the second biological near-infrared(NIR-?,1000-1350 nm)window photothermal reagent for the photothermal therapy of tumors has great potential for clinical application.In this work,a thieno-isoindigo derivative-based semiconducting polymer,PBTPBF-BT,were formulated into PEGylated nanoparticles(NPPBTPBF-BT).We use drug-loaded nanoparticles(NPPBTPBF-BT)for photothermal therapy and photoacoustic imaging.Mainly includes the following two aspects:(1)According to the literature,the semiconducting polymer PBTPBF-BT was synthesized by Stille cross-coupling reaction.The polyphosphate nano-system containing PBTPBF-BT semiconducting polymer was constructed by single emulsion method,labeled as NPPBTPBF-BT.We examined the maximum absorption wavelength of NPPBTPBF-BT was ~1107 nm.Here,we prove that NPPBTPBF-BT has significant light stability,high light-to-heat conversion efficiency and good biocompatibility.At the same time,NPPBTPBF-BT has obvious photothermic toxicity under 1064 nm infrared light irradiation and can effectively kill MDA-MB-231 tumor cells in the cytotoxicity experiment.Therefore,PBTPBF-BT is a new type photothermal agent.(2)Based on the above experimental results,we further studied the antitumor effect of NPPBTPBF-BT in vivo.The results show that NPPBTPBF-BT can exert antitumor effect only under the condition of 1064 nm near-infrared light irradiation,and the antitumor effect is more obvious with the increase of near-infrared light intensity.What's more,NPPBTPBF-BT light-heat conversion process accompanied by ultrasound signals,the signals can be used for tumor photoacoustic imaging.We constructed an imaging model of tumor mice to detect the imaging time and effect of NPPBTPBF-BT in vivo,and proved that NPPBTPBF-BT has excellent photostability for photoacoustic imaging,suggesting the great probability of using NPPBTPBF-BT for in vivo PA imagingguided PTT in the NIR-? window.