Breakthrough in cancer therapy: lutetium texaphyrin-celecoxib conjugate for immune and photodynamic treatment.

Abstract

Immuno-photodynamic therapy (IPDT) has become a promising approach for cancer treatment. Innovative photosensitizers are essential to fully realize the potential of IPDT, specifically the complete elimination of tumors without recurrence. In this context, Jong Seung Kim et al. introduce a small molecule photosensitizer conjugate, LuCXB. This IPDT agent combines a celecoxib (cyclooxygenase-2 inhibitor) moiety with a near-infrared absorbing lutetium texaphyrin photocatalytic core. In aqueous solutions, the two components of LuCXB self-associate through inferred donor-acceptor interactions. As a result of this intramolecular association, LuCXB generates superoxide radicals (O₂^-˙) via a type I photodynamic pathway upon irradiation with 730 nm light. This serves as a primary defense against the tumor and enhances the IPDT effect. For in vivo applications, they developed a CD133-targeting, aptamer-functionalized exosome-based nanophotosensitizer (Ex-apt@LuCXB) aimed at targeting cancer stem cells. Ex-apt@LuCXB demonstrated excellent photosensitivity, satisfactory biocompatibility, and strong tumor-targeting capabilities. Under photoirradiation, Ex-apt@LuCXB amplifies IPDT and produces significant antitumor effects in liver and breast cancer mouse models. The therapeutic outcomes are attributed to a synergistic mechanism that combines antiangiogenesis with photoinduced cancer immunotherapy.