NIR-laser-triggered smart full-polymer nanogels for synergic photothermal-/chemo-therapy of tumors

摘要

Near infrared (NIR, λ = 700–1100 nm) laser-triggered drug delivery systems (DDs) have attracted great interest for the synergic photothermal-/chemo-therapy of tumors, and a prerequisite for their development is to obtain biocompatible and efficient nanoplatforms that possess excellent photothermal and controllable (on/off) drug-release abilities. Herein, we have designed and fabricated full-polymer smart nanogels (PNA–CS–PPy–DOX) as novel NIR-DDs, by using polypyrrole (PPy) as the photothermal agent, PNA–chitosan (PNA–CS) with a lower critical solution temperature (LCST) of 42 °C as the carrier and the doxorubicin (DOX) as the model of the anticancer drugs. The aqueous dispersion of PNA–CS–PPy–DOX shows increased photoabsorption with a wavelength from 600 to 1100 nm. The temperature of its aqueous dispersions (PPy concentration: 1–20 μg mL ~(?1) ) goes up quickly from room-temperature to 32.4–60.3 °C in 5 min under the irradiation of a 915 nm laser (intensity: 2.0 W cm ~(?2) ), verifying the excellent photothermal performance. To simulate the in vivo drug delivery, a typical aqueous PNA–CS–PPy–DOX (～10 mg mL ~(?1) ) dispersion is covered by chicken skin as the model of biological tissue. After the irradiation of the 915 nm laser (intensity: 2.0 W cm ~(?2) ), the temperature of the dispersion goes up to higher than 42 °C (LCST of PNA–CS), resulting in the release of the drug. As a result, the cumulative release of DOX from PNA–CS–PPy–DOX increases from 1.67% (at 0 min) to 48.53% (at 14 min of irradiation), indicating the excellent intelligence and controllability. Subsequently, the PNA–CS–PPy–DOX dispersion is injected into the tumor of the mice. Under the irradiation of the 915 nm laser, the cancer cells can be efficiently destroyed, and the tumor suffers significant ablation, indicating the excellent synergic photothermal-/chemo-therapy effects compared with the single photothermal therapy or chemotherapy effect. Therefore, the present PNA–CS–PPy–DOX nanogels have great superiority as a biocompatible and efficient nanoagent for the synergic photothermal-/chemo-therapy of tumors.