Efficient hydroxyl radical generation of an activatable phthalocyanine photosensitizer: oligomer higher than monomer and nanoaggregate

Abstract

It remains a challenge to develop a single-component organic photosensitizer that efficiently produces hydroxyl radicals (˙OH) without oxygen involvement, especially while maintaining tumor-targeting capability. Herein, we propose an intelligent molecular design strategy whereby a tumor-targeted phthalocyanine is initially ˙OH-free and can be activated by overexpressed β-nicotinamide adenine dinucleotide sodium salt hydrate (NAD(P)H) in hypoxic tumors to efficiently produce ˙OH under light irradiation. Furthermore, the oligomer models based on the phthalocyanine molecules were constructed by a supramolecular regulation strategy, which were in an intermediate state between monomer and nanoaggregate, to achieve enhanced ˙OH generation. The level of NAD(P)H in cancer cells can be exhausted through two pathways, including spontaneous redox and the photocatalytic redox of phthalocyanines. As a result, the in vivo and in vitro assays illustrated that the oligomeric phthalocyanine containing N–O units (OligPcNOB) can specifically target cancer cells and tumor tissue with overexpressing biotin receptors. OligPcNOB exhibited significant photocytotoxicity even in an extremely low oxygen environment and successfully inhibited tumor progression.