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 100x 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.