Biotinylated platinum(IV)-conjugated graphene oxide nanoparticles for targeted chemo-photothermal combination therapy in breast cancer

Abstract

Graphene oxide (GO) and GO-based nanocomposites are promising in drug delivery and photothermal therapy due to their exceptional near-infrared optical absorption and high specific surface area. In this study, we have effectively conjugated an oxaliplatin (IV) prodrug, PEGylated graphene oxide, and PEGylated biotin (PB) in a single platform for breast cancer treatment. This platform demonstrates promising prospects for targeted drug delivery and the synergistic application of photothermal-chemotherapy when exposed to NIR-laser irradiation. The resulting nanocomposite (GO(OX)PB (1/1/0.2) NPs) displayed an exceptionally large surface area, minimal particle size (195.7 nm), specific targeting capabilities, a high drug load capacity (43.56 %) and entrapment efficiency (89.48 %) and exhibit excellent photothermal conversion efficiency and photostability when exposed to NIR-laser irradiation (808 nm). The therapeutic effectiveness was assessed both in vitro and in vivo conditions employing human breast cancer cells (MCF-7), mouse mammary gland adenocarcinoma cells (4T1), and 4T1-Luc tumor-bearing mouse models. The findings demonstrated that GO(OX)PB (1/1/0.2) NPs (+L) were highly effective in causing significant cytotoxicity, G2/M phase cell cycle arrest, ROS generation, mitochondrial membrane depolarization, apoptosis, and photothermal effect. This resulted in a greater percentage of cell death compared to free OX, GO(OX)PEG (1/1/0.2) NPs (±L), and GO(OX)PB (1/1/0.2) NPs (−L). The in vivo therapeutic studies on 4T1-Luc tumor-bearing mice revealed that a combination of GO(OX)PB (1/1/0.2) NPs (+L) caused complete disappearance of the tumor, no tumor recurrence, prolonged survival, reduced lung metastasis, and mitigated nephrotoxicity. The serum and blood analysis demonstrated minimal systemic toxicity of GO(OX)PB (1/1/0.2) NPs. The developed nanoplatform, in this context, may serve as a potential nanomedicine to address conventional nephrotoxicity in breast cancer and prevent metastasis by combining chemo-photothermal therapy.