Efficient and highly biocompatible 8-arm PEG-Chlorin e6 nanosystems for 2-photon photodynamic therapy of adrenergic disorders

Abstract

Two highly biocompatible nanosystems have been designed, synthesized, characterized, and demonstrated in vitro for enhanced 2-photon photodynamic therapy (2p-PDT) of adrenergic disorders. These systems consist of a compact, star-shaped, 8-arm poly(ethylene glycol) (8-arm PEG) core, to which are attached (1) a natural photosynthetic unit, Chlorin e6 (Ce6), and (2) a choice of two newly synthesized meta-iodobenzylguanidine (MIBG) moieties modified with a 3-mercaptopropionic amide functional linking group “3-MPAM” : “MIBG-3-MPAM” or “BG-3-MPAM”. A modest self-assembly of these multifunctional nanosystems promotes a 2-photon absorption cross-section (TPACS) enhancement while retaining a high level of reactive oxygen species (ROS) generation. The photodynamic effect of the 8-arm PEG-Ce6-dMIBG nanosystem is shown to be highly effective, while employing harmless, but deep-tissue penetrating, near-infrared (NIR) photons in vitro on a neuroblastoma cell line. Thus, this new nanosystem with the dMIBG modification shows high promise towards 2-photon photodynamic therapy of adrenergic diseases, with a wider application on other hard-to-treat diseases.