Smart J-aggregate of cyanine photosensitizer with the ability to target tumor and enhance photodynamic therapy efficacy

Abstract Photodynamic therapy (PDT) has been demonstrated to be effective for cancer treatment. Design of photosensitizers (PS) featuring tumor targeting, long excitation wavelengths, and high singlet oxygen quantum yields (Φ(1O2)) is the crucial point of highly efficient PDT. However, it is especially difficult to integrate above features into one photosensitizer. Herein, we put forwards a PS J-aggregation method, simultaneously endowing PS with the ability of tumor targeting, the red-shift of spectra, and the increase of Φ(1O2). Cyanine PS 4-((E)-3-((E)-5-iodo-1,3,3-trimethylindolin -2-ylidene)prop-1-en-1-yl)-1-methylquinolin-1-ium iodide (IDMQ) is firstly designed and synthesized by us. IDMQ can form smart response-type J-aggregates under the control of negatively charge in microenvironments. In blood, IDMQ J-aggregates target tumor via “enhanced permeability and retention (EPR)” effect. Then the intracellular IDMQ J-aggregates assembled by RNA facilitate the red shift of absorption peak with deeper penetration, and compared to free state IDMQ, improve the Φ(1O2), resulting in the bathochromic shift of optimal PDT wavelength from 630 (free state IDMQ) to 700 nm (IDMQ J-aggregates). This intelligent J-aggregation method establishes a promising way for endowing photosensitizer with the ability of tumor-targeting and the synchronous improvement of PDT efficacy and further boosts the development of PDT.