1064 nm activatable semiconducting polymer-based nanoplatform for NIR-II fluorescence/NIR-II photoacoustic imaging guided photothermal therapy of orthotopic osteosarcoma

As a promising anti-tumoral approach, photothermal therapy (PTT) with NIR-II (1000–1700 nm) absorption could penetrate deeper and generate more efficient hyperthermia in contrast to traditional PTT under 808 nm irradiation. As for optical tracking, NIR-II fluorescence imaging (FI) and NIR-II photoacoustic imaging (PAI) are the two emerging research hotspots. Unfortunately, each single modality has its intrinsic limitations and current research to integrate them in one-component system is still in infancy. Our development of all-in-one nanoplatforms aims to ultimately improve the efficacy of targeted hyperthermia, and incorporate the benefits of NIR-II FI and NIR-II PAI for tracking guidance. Herein, we designed a novel semiconducting polymer P2, and further encapsulated it with amphiphilic PEGylated phospholipid modified with a targeting peptide RGD to ultimately generate P2 based nanoparticles (P2NPs). As a single-component phototheranostic nanoplatform, P2NPs possessed intense NIR-II absorption, excellent NIR-II fluorescence, strong NIR-II PA signals, and high local hyperthermia capability simultaneously. Notably, due to the favorable binding capacity to osteosarcoma (OS) cells, in vitro studies revealed outstanding PTT efficacy of P2NPs against 143B cells under 1064 nm laser. Further work validated excellent dual-modal NIR-II FI/NIR-II PAI tracking and strong PTT tumor ablation in both subcutaneous and orthotopic OS mice models with negligible biotoxicity in vivo. Consequently, these findings warranted P2NPs as a promising 1064 nm activatable all-in-one nanoplatform to perform dual-modal NIR-II FI/NIR-II PAI-guided orthotopic tumoral treatment, providing a new approach for theranostics, therapeutic tracking, and the beyond in other diseases.