Intraparticle Molecular Orbital Engineering of Semiconducting Polymer Nanoparticles as Amplified Theranostics for <i>in Vivo</i> Photoacoustic Imaging and Photothermal Therapy

TLDR

Optical theranostic nanoagents that integrate imaging and therapy can offer cost‑effective precision medicine, but clinical translation demands biocompatibility and high imaging/therapy performance. This work introduces an intraparticle molecular‑orbital engineering strategy to simultaneously enhance photoacoustic brightness and photothermal therapy efficacy of semiconducting polymer nanoparticles for in vivo cancer imaging and treatment. The engineered SPNs comprise a binary nanostructure of a near‑infrared absorbing polymer and ultrasmall carbon dots that undergo photoinduced electron transfer, boosting heat generation. The intraparticle optoelectronic interaction raises heat generation, increasing photoacoustic signal by 2.6‑fold and photothermal temperature by 1.3‑fold, enabling superior imaging and tumor ablation in mice and establishing a purely organic theranostic platform with a molecular guideline for amplifying light‑based imaging and therapy.

Abstract

Optical theranostic nanoagents that seamlessly and synergistically integrate light-generated signals with photothermal or photodynamic therapy can provide opportunities for cost-effective precision medicine, while the potential for clinical translation requires them to have good biocompatibility and high imaging/therapy performance. We herein report an intraparticle molecular orbital engineering approach to simultaneously enhance photoacoustic brightness and photothermal therapy efficacy of semiconducting polymer nanoparticles (SPNs) for in vivo imaging and treatment of cancer. The theranostic SPNs have a binary optical component nanostructure, wherein a near-infrared absorbing semiconducting polymer and an ultrasmall carbon dot (fullerene) interact with each other to induce photoinduced electron transfer upon light irradiation. Such an intraparticle optoelectronic interaction augments heat generation and consequently enhances the photoacoustic signal and maximum photothermal temperature of SPNs by 2.6- and 1.3-fold, respectively. With the use of the amplified SPN as the theranostic nanoagent, it permits enhanced photoacoustic imaging and photothermal ablation of tumor in living mice. Our study thus not only introduces a category of purely organic optical theranostics but also highlights a molecular guideline to amplify the effectiveness of light-intensive imaging and therapeutic nanosystems.