Key Words:CANCER; CYCLOOXYGENASE-2; NANOPARTICLES; PENETRATION; PH

Abstract:Photothermal therapy has become a promising approach as precision medicine to allow spatial control of therapeutic effect only in the site of interest. However, the full potential of PTT has not been real-ized due to the lack of simple photosensitizers (PSs) that can overcome multistage biological barriers and improve theranostic efficiency. Here, we develop a small molecule-based PS to enhance tumor-specific PTT by programming multistage transport and activation properties in molecular architecture. This PS can self-assemble into stable nanoparticles that accumulate passively in tumor, and then actively in-ternalize through ligand-mediated endocytosis. Subsequently, the programmable degradable linkers are selectively cleaved, enabling size shrinkage for better tumor penetration, binding albumin to enhance the near-infrared fluorescence for low-background imaging, and activating photothermal conversion for tumor suppression. The self-delivery process can be programmed, representing the first multistage small -molecule nano-photosensitizer that overcomes multiple biological barriers and improves the PTT index of tumor.Statement of Significance Photothermal therapy has become a promising approach as precision medicine, but has not been realized due to the lack of simple photosensitizers that can overcome multistage biological barriers and improve theranostic efficiency. In this contribution, we solve this dilemma by developing a small molecule-based photosensitizer by programming multistage transport and activation properties in molecular architecture, which could self-assemble into stable nanoparticles that accumulate passively in tumor, and actively in-ternalized through ligand-mediated endocytosis. Subsequently, the programmable activation by ROS trig-gered size reduction for tumor penetration and minimized the phototoxicity to normal tissue. The acti-vatable fluorescence and photothermal properties made the photosensitizer intrinsically suitable for mul-timodal imaging-guided PTT, providing a promising supramolecular nanomedicine towards tumor precise diagnosis and therapy.(c) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Volume:157

Issue:

Translation or Not:no