Copper sulfide nanoparticles coated with Fe-EGCG networks for targeted MR imaging and chemo/photothermal/chemodynamic synergetic therapy of tumors

Abstract

Despite the extensive application of copper sulfide nanoparticles (CuS NPs) as photothermal therapeutic agents in biomedical fields, their efficient tumor theranostics via specific delivery and multimodal therapy remains a formidable challenge. In this study, functional CuS NPs coated with iron ( Fe)-(-)-epigallocatechin gallate (EGCG) metal polyphenolic networks (MPNs) were synthesized for targeted magnetic resonance (MR) imaging-directed chemo/photothermal/chemodynamic synergetic therapy of tumors. The nanocomposites were prepared using polyethylene glycol (PEG)-conjugated folic acid (FA) and fluorescein isothiocyanate (FI) pre-modified polyethylenimine (PEI.NH₂) as a nanotemplate, followed by in situ formation of CuS NPs within its internal cavity, acetylation of surface amines, and Fe-EGCG MPNs coating. The resulting FA-CuS PENs@Fe-EGCG nanocomposites with an average diameter of 10.81 nm exhibit eminent photothermal conversion efficiency (51.1%), great colloidal and photothermal stability, favorable T₁ relaxivity (r₁ = 4.8005 mM ^-1 s ^-1 ), pH/near infrared (NIR) laser dual-responsive drug release characteristics, and enhanced Fenton reaction catalytic activity. The active targeting effect of FA enables the specific cellular uptake of FA-CuS PENs@Fe-EGCG nanocomposites by cancer cells overexpressing FA receptors, facilitating targeted tumor T₁-weighted MR imaging in vitro and in vivo. Notably, EGCG and NIR laser irradiation could enhance Fe-mediated Fenton reaction efficiency, increasing hydroxyl radical (•OH) production and potentiating chemodynamic therapy efficacy. Through effectively generating reactive oxygen species (ROS), consuming glutathione (GSH), accumulating lipid peroxidation (LPO), and promoting cancer cell apoptosis under laser irradiation, the FA-CuS PENs@Fe-EGCG nanocomposites could exert superior tumor suppression efficacy in the 4T1 xenograft mice model by targeted chemo/photothermal/chemodynamic synergetic therapy. This work presents a succinct design of advanced nanocomposites incorporating CuS NPs and MPNs, offering a promising strategy for tumor theranostics.