A tailored nanosheet decorated with a metallized dendrimer for angiography and magnetic resonance imaging-guided combined chemotherapy

Abstract

Considering the chemical exchange between gadolinium centers and water protons, nanosystems comprising gadolinium conjugated with high specific area nanocarriers might serve as more robust clinical tools for diagnosis and imaging-guided therapy. Herein, a pH-responsive nanosystem containing graphene oxide conjugated with a folic acid- and gadolinium-labeled dendrimer (FA-GCGLD) to boost its T₁ contrast ability was developed, and doxorubicin (DOX) and colchicine (COLC) were efficiently loaded onto this nanosystem (FA-GCGLD-DOX/COLC). This nanosystem showed a prominent T₁ contrast with an ultrahigh relaxivity of up to 11.6 mM⁻¹ s⁻¹ and pH-responsive drug release behavior. HepG2 cells treated with FA-GCGLD-DOX/COLC were efficiently inhibited, and the cell contrast was enhanced. In vivo, the tumor accumulation of FA-GCGLD-DOX/COLC significantly increased, thereby facilitating the systemic delivery of particles and exerting tumor growth inhibition and an enhanced tumor contrast effect. Moreover, compared to free drugs, FA-GCGLD-DOX/COLC effectively decreased the drug resistance of the tumor, thereby improving the cancer chemotherapeutic efficacy. In addition, injecting rats with FA-GCGLD afforded excellent magnetic resonance angiography (MRA) images with high-resolution vascular structures because of the long blood circulation time of FA-GCGLD. Thus, this study provides a powerful tool for diverse applications in the biomedical field, including accurate diagnosis and chemotherapy of tumors and the detection of cardiovascular diseases.