Thermosensitive hydrogel-functionalized gold nanorod/mesoporous MnO₂ nanoparticles for tumor cell-triggered drug delivery

MnO2 owns distinct redox, imaging, and degradable properties corresponding to the tumor microenvironment. However, the onefold structure and non-modifiable property cause many obstacles to anticancer applications. In this report, we first prepared a typical core-shell gold nanorod (GNR)/manganese dioxide (MnO2) nanoparticles (GNR/MnO2 NPs). Interestingly, the MnO2 had a mesoporous channel and modifiable hydroxyl group (-OH). Here, the unique '-OH' groups were modified and further grafted with poly(N-isopropylacrylamide-co-acrylic acid) (PNA). As a dual-sensitive hydrogel, it was selected as the thermal/pH-sensitive component in the hybrid nanoparticles (GNR/MnO2/PNA NPs). The anticancer drug doxorubicin hydrochloride (DOX) was selected and loaded into the hybrid nanoparticles (GNR/MnO2/PNA-DOX NPs). The GNR/MnO2/PNA NPs achieved satisfying drug-loading efficiency and glutathione (GSH)/pH/thermal-responsive drug-controlled release. As a side benefit, the GNR/MnO2/PNA NPs showed potential as excellent near-infrared (NIR)-excited nanoplatforms for photothermal therapy (PIT). Delightedly, the studies demonstrated that the GNR/MnO2/PNA-DOX NPs showed a noticeable killing effect on tumor cells, whether it is tumor cell-triggered drug release or photothermal effect. Besides, it not only could enhance mitochondrial damage but also could inhibit the migration and invasion of tumor cells. Quite the reverse, it had little negative impact on normal cells. The feature can prevent anticancer drugs and nanoparticles from killing normal cells. Consequently, GNR/MnO2/PNA NPs have potential applications in drug delivery and synergistic therapy due to these advantageous features.