Self-Adaptive Photodynamic-to-Photothermal Switch for Smart Antitumor Photoimmunotherapy

Photodynamic therapy (PDT) and photothermal therapy (PTT)
possess
different merits in cancer phototherapy, but the tumor microenvironment
becomes unfavorable during the phototheranostic progress. Herein,
we report a self-adaptive cyanine derivative Cy5-TPA with
the PDT-dominated state to PTT-dominated state autoswitch feature
for enhanced photoimmunotherapy. The incorporation of rotatable triphenylamine
(TPA) moiety renders Cy5-TPA with the temperature or
intramolecular-motion regulated photoactivities, which shows preferable
reactive oxygen species (ROS) generation at lower temperature while
stronger photothermal conversion at higher ones. Such a promising
feature permits the in situ switch from PDT-dominated state to PTT-dominated
state along with intratumoral temperature increase during laser irradiation,
which also works in line with the concurrently reduced intratumoral
oxygen level, exhibiting a self-adaptive phototherapeutic behavior
to maximize the phototherapeutic antitumor outcome. Most importantly,
the self-adaptive PDT-dominated state to PTT-dominated state switch
also facilitates the sequential generation and release of damage-associated
molecular patterns during immunogenic cell death (ICD). Hence, Cy5-TPA demonstrates excellent photoimmunotherapy performance
in ICD induction, dendritic cell maturation, and T cell activation
for tumor eradication and metastasis inhibition.