Experimental study of dendrimer-based nanoparticles with RGD-peptide for anticancer radionuclide therapy

Abstract

Radionuclide therapy (RNT) is an effective modality for treating multiple metastases in patients with cancer. The list of malignancies that can be managed with RNT expands with the arrival of novel tumoritropic radiopharmaceuticals (RP). A versatile delivery platform capable of carrying various therapeutic and diagnostic radionuclides, as well as vector molecules needed to achieve sufficient specificity to tumor cells and ensure therapeutic efficacy may hold great promise for radiation therapy. The aim of this work was to assess the performance of a delivery system based on the original dendrimer. The dendrimer demonstrated low toxicity in mice (LD50 was 779 ± 111 mg/kg). To study the specificity of the dendrimer to tumor cells and its therapeutic efficacy, we used a nanostructure (NS) composed of the dendrimer itself, the RGD peptide and 188Re (188Re-NS). Lewis lung carcinoma LLC1 was used as a tumor model. The biodistribution analysis revealed that the compound effectively accumulated in the tumor demonstrating a tumor-to-normal ratio >1 (relative to healthy organs and tissues) and retention time of at least 6 hours. Injections of 185 MBq/kg 188Re-NS caused a statistically significant inhibition of tumor growth (p < 0.05) by day 7 following the injection (Т/С = 5%), which remained stable for 6 days. Our findings suggest that the proposed dendrimer is a promising platform for RP delivery.