Engineering of 177Lu-labeled gold encapsulated into dendrimeric nanomaterials for the treatment of lung cancer

As a novel type of theranostic radioactive agents, Lu-177-labeled nanomaterials conjugated to macromolecules have been described. The study aimed to fabricate PAMAM-G4-(Lu-177-dendrimer)-bombesin-folate in the dendrimeric cavity, assess the radiopharmaceutical ability for specifically targeted radiotherapy and simultaneously detects gastrin-releasing peptide receptors (GRPR) and folate receptors (FRs) overexpressed in lung carcinoma cells, respectively. In an aqueous-basic media, p-SCN-benzyl-DOTA was conjugated to the dendrimer. This dendrimer was formed by activating the carboxylic acid groups of DOTA-folic acid and bombesin with HATU and conjugating them to develop the dendrimer. As part of this process, the conjugate was combined with 1% HAuCl4, added NaBH4 and filtered by ultrafiltration. Infrared, UV-Vis, TEM analysis, dynamic light scattering (DLS), and fluorescence spectroscopy were employed to observe the composition of the fabricated sample. Radio-labeled (LuCl3)-Lu-177 was used to label the conjugate, which was then evaluated using the radio-HPLC method. Findings demonstrated dendrimeric functionalization with remarkable radiochemical composition purity up to >96%. Because of fluorescence studies, it was determined that the occurrence of AuNMs in the dendrimeric cavities gives beneficial photo-physical characteristics to the radiopharmaceutical for bio-imaging. HEL-299 lung cancer cells exhibited a selective absorption of the drug (%). It might be helpful as nuclear and optical imaging agents for lung cancers that overexpress FRs and GRPR and as a specific target for radiation therapy if combined with folate-bombesin.

Automated summary

A novel type of theranostic radioactive agents, Lu-177-labeled nanomaterials conjugated to macromolecules have been studied for targeted radiotherapy and receptor detection in lung carcinoma cells. The fabricated sample showed remarkable radiochemical composition purity and beneficial photo-physical characteristics for bio-imaging, making it a potential nuclear and optical imaging agent for lung cancer. Combining with folate-bombesin might provide a specific target for radiation therapy.