RGD/CTX-conjugated multifunctional Eu–Gd2O3 NRs for targeting detection and inhibition of early tumor

Abstract

Glioblastoma is currently the most common and lethal brain tumor, so accurate detection and effective therapy at the early glioblastoma stage is crucial. Herein, multifunctional Eu–Gd₂O₃ nanorods (NRs) with good paramagnetic and luminescence properties were fabricated through a hydrothermal method and a subsequent calcination technique, and exhibited good T₁-weighted magnetic resonance (MR) imaging (r₁ = 5.13 Gd mM⁻¹ s⁻¹) and cell-luminescence imaging properties. Then, Eu–Gd₂O₃ NRs were coated with difunctionalized polyethylene glycol (Mal-PEG-NHS), and subsequently conjugated through thiolation with arginine–glycine–aspartic (RGD) and chlorotoxin (CTX), respectively. The results of the cell test indicated that RGD/CTX-conjugated Eu–Gd₂O₃ NRs (RGD-NRs-CTX) could specifically target and adhere on U251 cells, leading to cellular apoptosis. The in vivo investigation revealed that RGD-NRs-CTX possessed no tissue/organ toxicity and a long blood circulation time. The results of in vivo MR imaging showed a significant preferential targeting and accumulation of RGD-NRs-CTX onto the early tumor, and in vivo luminescence imaging displayed a good infiltration capacity in tumor regions. Based on a superimposed targeting property of CTX and RGD, the results of everyday tail-vein injection suggested that RGD-NRs-CTX could effectively inhibit early tumor growth, without any damage to normal tissues/organs. Therefore, these results demonstrate that RGD-NRs-CTX are promising candidates for simultaneous targeting detection and therapy for early tumor.