Flexible Synthesis Scheme and Application of AuNP Surface-Conjugatable Metaiodobenzylguanidine Derivatives for Enhanced Cellular Internalization

A synthesis of two metaiodobenzylguanidine (MIBG) derivatives is reported: N -[4-(guanidinomethyl)-2-iodophenyl]-3-mercaptopropanamide (MIBG-3-MPAM) and N -[4-(guanidinomethyl)phenyl]-3-mercaptopropanamide (BG-3-MPAM). The design of these molecules allows for their conjugation to a wide range of nanocarriers, such as pulsed-laser ablation (PLA)-synthesized gold nanoparticles (AuNPs), which are utilized here to assess uptake into neuroblastoma (NB), HeLa, and HEK cell lines. Through dark-field imaging and quantitative inductively coupled plasma mass spectrometry (qICP-MS), the MIBG derivatives are found to enhance total AuNP uptake in vitro by over 100× at sufficiently high molar ratios across cell lines, and the iodine atom is found to play an important role in further enhancing the uptake efficiency.