Precise Photodynamic Therapy Of Oesophageal Cancer Using Bioharmonophores

Bioharmonophores are a new class of biodegradable optical imaging nanoprobes that generate a bright second harmonic (SHG) signal without blinking, bleaching, or saturation. They consist of polymer-encapsulated, self-assembling peptides that create this strong SHG signal by combining two photons to form a photon with twice the energy and half the wavelength. Oesophageal cancer is the eighth most common cancer worldwide, yet the sixth leading cause of cancer death due to poor prognosis and high mortality rates. Survival rates have remained unsatisfactory; highlighting the need to improve current therapeutic approaches. Photodynamic therapy (PDT) is a non-invasive treatment for oesophageal adenocarcinoma (OAC). This study enhanced PDT using bioharmonophores dual-conjugated with met-pep1 (targeting HGFR overexpressed in OAC) and protoporphyrin IX (PpIX). This conjugation increased bioharmonophore accumulation in OAC cells, enabling precise, targeted PDT. Upon two-photon illumination, OAC cells and organoids produced greater reactive oxygen species and experienced greater cell death, improving treatment efficacy.