DOX/ICG Coencapsulated Liposome-Coated Thermosensitive Nanogels for NIR-Triggered Simultaneous Drug Release and Photothermal Effect

Chemo-photothermal therapy has shown enormous potential in treating cancer. To achieve the chemo-photothermal synergistic effect, an efficient nanoparticulate system with the ability for simultaneous codelivery of chemotherapeutic drug and photothermal agent as well as photothermal-triggered drug release is highly desirable. Herein, an in situ polymerization within liposome template was designed to prepare liposome-coated poly(N-isopropylacrylamide-co-acrylamide) (P(NIPAM-co-AAM)) nanogels, which can efficiently coencapsulate a NIR dye indocyanine green (ICG) and high amount of doxorubicin hydrochloride (DOX). The DOX/ICG coloaded hybrid nanogels, denoted as DI-NGs@lipo, integrated the desirable functions of PEGylated liposomes and thermosensitive nanogels. The PEGylated liposome shell provided excellent storage stability, hemodynamic stability, and fluorescence stability. Meanwhile, the thermosensitive P(NIPAM-co-AAM) nanogels core endowed DI-NGs@lipo with volume phase transition temperature (VPTT) at about 40 °C, allowing for thermo-controlled transformation and drug release. The significant photothermal effect of DI-NGs@lipo and the simultaneous hyperthermia-triggered DOX release were observed under NIR light irradiation. The DI-NGs@lipo was demonstrated to be uptaken by 4T1 murine breast cancer cells via endocytosis, enhancing the distribution of DOX in the cell nucleus. Compared with chemo or photothermal treatment alone, the combination treatment of DI-NGs@lipo with NIR light irradiation induced significantly higher cytotoxicity to 4T1 cells, demonstrating the chemo-photothermal synergistic therapeutic effects on tumor cells. In a word, the strategy provided here offers a facile approach to develop a multifunctional nanoplatform for codelivery of DOX and ICG, which can synergistically improve the cancer-cell-killing efficiency, demonstrating great potential in chemo-photothermal therapy.