177Lu Radiolabeled Polydopamine Decorated with Fibroblast Activation Protein Inhibitor for Locoregional Treatment of Glioma.

Radionuclide therapy is expected to be a powerful tool for glioma treatment. Here, we introduced a novel nuclear nanomedicine based on polydopamine (PDA), incorporating fibroblast activation protein inhibitor (FAPI) and macrocyclic chelator (DOTA) for specific cancer targeting and ¹⁷⁷Lu labeling. The synthesized nanoradiopharmaceutical, ¹⁷⁷Lu-DOTA-PEG-PDA-FAPI, exhibits good stability in serum, saline and PBS over 5 days. ¹⁷⁷Lu-DOTA-PEG-PDA-FAPI shows efficient specific uptake and internalization when incubated with U87MG cells. In vivo distribution visualized prominent accumulation and long retention ability of ¹⁷⁷Lu-DOTA-PEG-PDA-FAPI at tumor sites after local administration. Moreover, ¹⁷⁷Lu-DOTA-PEG-PDA-FAPI has satisfactory antitumor ability without apparent toxic and side effects observed from therapy assay and H&E staining. This study highlights the feasibility of using PDA as a nanocarrier for glioma endoradiotherapy by targeting fibroblast activation protein.