TLR-7/8 Agonist-Loaded Polypyrrole-Based Theranostic Nanovaccine for Second Near-Infrared Photothermal Immunotherapy of Cancer

Functionalized theranostic agents have the potential to be an effective tool for targeting tumor cells with an effective response in cancer imaging and therapy. Particularly, near-infrared (NIR) light is extremely advantageous and can penetrate deeply into biological tissues with minimum attenuation and photodamage to cells. The major impediment to the translation of research into clinical applications is toxicity and long-term body retention. Designing renal clearable and theranostic qualities in a single nanoplatform remains the biggest challenge. Especially, nanomaterials have optical absorption in the second biowindow (NIR-II) with deep penetration and less tissue scattering. Photothermal therapy (PTT), which uses hyperthermia produced by photothermal agents (PTAs) that convert light irradiation to ablate tumors, has received great attention due to its noninvasiveness. Herein, we developed an NIR-II-responsive ultrasmall polypyrrole (PPy)-based theranostic agent conjugated with TAT peptide that has a unique nuclear-targeting property that allows for efficient nuclear-targeted photothermal ablation and immunogenic cell death (ICD). Furthermore, PPy decorated with hyaluronic acid (HA)-loaded toll-like receptor 7/8 immune-activating drug resiquimod (R848), a synthetic agonist for the maturation of dendritic cells. Therefore, the prepared nanocomposite leads to effective tumor cell nuclear ablation, together with a photothermal immune response and renal clearance. This strategy may provide another avenue for highly efficient cancer theranostic nanovaccines.