NIR-II absorptive dithienopyrrole-thiadiazolobenzotriazole conjugated polymer for photoacoustic imaging-guided glioblastoma multiforme photothermal therapy

The development of new diagnostic imaging and precise treatment methods for glioblastoma multiforme (GBM) is significant to improve patients' quality of life and prolong their survival time. Herein, we pro-posed a photoacoustic imaging (PAI)-guided GBM high-efficient photothermal therapy (PTT) based on a second near-infrared (NIR-II) absorptive polymer (PDTP-TBZ) conjugated with intense electron donor dithienopyrrole (DTP) and strong electron acceptor thiadiazolobenzotriazole (TBZ). By nanoprecipitation, PDTP-TBZ can form into nanoparticles (PT NPs), and c(RGDfK) cyclic peptide with integrin-specific target-ing was then modified on the surface of PT NPs to obtain the ability of active targeting GBM multifunc-tional nano-reagent (cRGD@PT NPs). Both in vitro and in vivo experiments demonstrated that cRGD@PT NPs as NIR-II GBM phototheranostic reagents can greatly improve the enrichment rate at tumor sites un -der PAI monitoring, and carry out precise NIR-II PTT with high effective tumor cell phototoxicity and high biological safety. Thus, cRGD@PT NPs have great potential for the future GBM phototheranostic applica-tion in clinic.Statement of significance In this work, we successfully constructed an intense electron donor dithienopyrrole (DTP) with a strong electron acceptor thiadiazolobenzotriazole (TBZ) into a novel NIR-II optical absorptive conjugated poly-mer (PDTP-TBZ). Then, the c(RGDfK) cyclic peptide was modified on the surface of PT NPs to obtain multifunctional nanodiagnostic reagents (cRGD@PT NPs) that can effectively target GBM neovasculariza-tion and tumor cells. Both in vitro and in vivo experiments demonstrate that cRGD@PT NPs possess high photothermal conversion efficiency and practical photoacoustic imaging capability under 1064 nm laser irradiation. The results of this work suggested that cRGD@PT NPs have great potential in efficient NIR-II PTT guided by accurate PAI, which provide a good perspective for the treatment and diagnosis of GBM.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Automated summary

In this study, a novel NIR-II optical absorptive conjugated polymer (PDTP-TBZ) was successfully constructed by combining an intense electron donor dithienopyrrole (DTP) with a strong electron acceptor thiadiazolobenzotriazole (TBZ). The c(RGDfK) cyclic peptide was then modified on the surface of PT NPs to obtain multifunctional nanodiagnostic reagents (cRGD@PT NPs) that can effectively target GBM neovascularization and tumor cells. Both in vitro and in vivo experiments demonstrated that cRGD@PT NPs possess high photothermal conversion efficiency and practical photoacoustic imaging capability under 1064 nm laser irradiation. The results of this study suggest that cRGD@PT NPs have great potential in efficient NIR-II PTT guided by accurate PAI, which provide a good perspective for the treatment and diagnosis of GBM.