Dual-Channel Theranostic System for Quantitative Self-Indication and Low-Temperature Synergistic Therapy of Cancer

A conventional theranostic system usually employs a single fluorescence channel to show the pharmacokinetic events, which usually fails to quantitatively reveal the true cumulative drug release and with low accuracy. Herein, indocyanine green (ICG) and chlorins e6 (Ce6) are selected not only as conventional photothermal/photodynamic agents, but also to offer two independent fluorescence channels to cross validate the authenticity of pharmacokinetic events and to quantitatively reveal cumulative drug release in tumor tissues in a "turn on" manner. Employing the Ca²⁺ of amorphous calcium carbonate as a reversible linker, the photosensitivity and fluorescence of Ce6 are physically quenched by ICG during circulation to reduce the side effect of photodynamic therapy (PDT) while being readily restored in tumor tissue to reveal the quantitative drug release. Most importantly, the combination of photothermal therapy (PTT) and PDT allows low-temperature synergistic therapy of cancer through the controlled expression of heat shock protein in cells and mild hyperthermia enhanced reactive oxygen species diffusion/penetration among cells. This work not only develops a facile approach to fabricate a dual-channel theranostic system to precisely indicate the accumulation and quantitative drug release in tumor tissue, but also presents a unique low-temperature synergistic strategy to destroy tumor in an effective and minimally invasive manner.