2,2,6,6-tetramethylpiperidin-1-oxyl: a new potential targeted ligand based on lipid peroxidation for targeted drug delivery

The side effects of chemotherapy drugs have prompted the development of targeted therapies. Distinctive abundance of lipid peroxidation (LPO) in tumour cells represents a potential target for drug delivery. However, LPO-based targeted ligands remain under-exploited. In this work, the targeting of 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO), was investigated within a mesoporous silica nanoparticle (MSN) loaded with doxorubicin (DOX) and connected with 4-NH₂-TEMPO obtaining DOX/MSN-TEMPO. A cellular uptake assay showed a faster uptake of DOX/MSN-TEMPO than blank group on Hela, L929 and 4T1 cells, revealing TEMPO's active targeting ability for tumour cells. After observing this phenomenon, the fabrication of a basic copolymer module carrying cyanine5.5 (Cy5.5) and TEMPO was reported. <i>In vivo</i> experiments were conducted on mouse MCF-7 tumour models, displaying selective aggregation of nano micelles at the tumour site and thereby verifying the broad applicability of TEMPO. Since the large amounts of LPO lead to the presence of numerous free radicals, whereas TEMPO, as a free radical capture agent, further selectively targets tumour cells. These findings verify the targeting ability of TEMPO for most tumour cells and collectively underscore the potential of TEMPO and analogous capture agents as innovative targeted ligands for drug delivery.