2,6-Pyridinedicarboxylic Acid Covalently Bound Polydopamine for Enhanced Tumor Photothermal Therapy in NIR-I and NIR-II

Polydopamine (PDA) possesses potential as a photothermal agent for tumor treatment owing to its photothermal capacity, chemical modifiability, excellent biocompatibility, and selective biodegradability. However, weak near-infrared (NIR) light absorption seriously hinders its actual utilization, especially in NIR-II. This study presents a novel molecularly modified PDA with remarkably increased NIR absorption and remarkably enhanced photothermal conversion capacity in both NIR-I and NIR-II. Dopamine monomers are covalently bound with elaborately selected 2,6-pyridinedicarboxylic acid (DPA) through an amidation reaction and then undergo an oxidative polymerization to form DPA-doped PDA nanoparticles (DPA-PDA NPs). By constructing donor-acceptor pairs and extending the conjugation length of molecular units, the energy band gap of DPA-PDA between the highest occupied molecular orbital and the lowest unoccupied molecular orbital is diminished from 0.77 to 0.45 eV, facilitating the electron low-energy transition. Meanwhile, the content of carbon-centered free radicals is obviously raised via suppressing their dimerization and quenching by the conjugation effect and steric hindrance effect, where the strengthened electron spin and vibration may promote charge and energy transfers, increasing and accelerating the excited electron nonradiative decay. As a result, the DPA-PDA NPs exhibit the enhanced NIR light absorption (196 and 205% over PDA) and much higher photothermal conversion efficiency (1.4 and 2.1 times that of PDA) under 808 and 1064 nm irradiation, respectively, achieving more effective tumor cells inhibition in vitro and tumor ablation in vivo. Interestingly, photothermal therapies with DPA-PDA for tumor-bearing mice emerge with higher tumor elimination (nearly 100%) under 1064 nm irradiation than that under 808 nm irradiation (94.3%), without recurrence within 20 days, which is attributed to both the enhanced photothermal capacity of DPA-PDA and the stronger tissue penetration ability of NIR-II. This design provides a new option to enhance the photothermal capacity of polydopamine as an applicative photothermal agent for tumor therapy.