Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of the State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian 350116, China; Institute of Oceanography, Minjiang University, Fuzhou, Fujian 350108, China. Electronic address: [Email]
The construction of multifunctional theranostic nanoplatforms to integrate accurate imaging and enhanced therapy to treat tumors is highly attractive but remains a challenge. Here, we developed a molybdenum disulfide (MoS2)-based hyaluronic acid (HA)-functionalized nanoplatform capable of achieving the targeted co-delivery of the gadolinium (Gd)-based contrast agents (CAs) and the anticancer drug gefitinib (Gef) for magnetic resonance imaging (MRI) and synergetic chemo-photothermal therapy of tumors. Gd3+ ions were coupled to HA-grafted MoS2 nanosheets with diethylenetriaminepentaacetic acid (DTPA) as a linker, followed by the incorporation of Gef. The resulting MoS2-HA-DTPA-Gd/Gef exhibited enhanced relaxivity, 3.3 times greater than that of the commercial CA DTPA-Gd, which facilitated the MRI in vivo. Moreover, the nanoplatform effectively converted the absorbed near-infrared (NIR) light into heat, which not only induced the photothermal ablation of cancer cells but also triggered the release of Gef from MoS2-HA-DTPA-Gd/Gef, enabling the synergetic chemo-photothermal therapy. The results of in vitro and in vivo experiments revealed that MoS2-HA-DTPA-Gd/Gef upon NIR irradiation effectively blocked the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway and activated apoptosis-related proteins to induce cell apoptosis and suppress cell proliferation, thus inhibiting the tumor growth in lung cancer cell-bearing mice. Taken together, this multifunctional theranostic nanoplatform has significant promise for the diagnosis and treatment of cancer.