Versatile gadolinium(III)-phthalocyaninate photoagent for MR/PA imaging-guided parallel photocavitation and photodynamic oxidation at single-laser irradiation.

Abstract

Current light-mediated photodynamic therapy (PDT) is far underutilized in clinical cancer treatment due to its low pharmacological effect. We herein proposed a new gadolinium(III)-phthalocyanine (GdPc)-enabled phototherapeutics, photoacoustic/dynamic therapy (PADT), towards in vivo solid tumors via parallel-produced photocavitation and photodynamic oxidation with excitation by a single pulsed laser. We demonstrated that pulsed irradiation of GdPc could simultaneously produce an intense acoustic effect and a high-level ¹O₂ quantum yield to afford mitochondrial damage and initiate programmed cell death. Under the guidance of magnetic resonance/photoacoustic dual-modal imaging, the mechanical oxygen-independent destruction of acoustic cavitation and the chemical damage of ¹O₂ were validated to afford combinatorial inhibition of tumors under either normal or hypoxic conditions after the agent delivered into the cancer cells by a pH-sensitive nanomicelle. The single-laser initiated PADT using GdPc as a versatile photoagent maximizes the use of light energy to minimize the dose requirement of oxygen and agent towards high therapeutic efficacy, surpassing dramatically over conventional PDT.