Phototheranostic Agents Based on Non-Ionic Heptamethine Cyanine for Realizing Synergistic Cancer Phototherapy.

Asymmetrical heptamethine cyanine with near-infrared (NIR) absorption has been used for photothermal therapy (PTT) of cancer. Aiming to overcome the drawbacks caused by the high temperature of PTT, the development of asymmetrical heptamethine cyanine with photothermal and photodynamic properties is still an attractive strategy. Different from the traditional method of the heavy atom effect, in this work, the carboxyl or sulfonic groups were introduced into the indole ring or branch chain of asymmetrical heptamethine cyanine to afford a series of new phototherapy agents. Compared with the sulfonic group (BHS-Et, SY-SO 3 , and BHS-SO 3 ), the introduction of the carboxyl group (BSS-Et and SY-COOH) could enhance the photodynamic characteristics of asymmetrical heptamethine cyanine and maintain its photothermal properties. After being encapsulated by DSPE-PEG 2000 , BSS-Et NPs exhibited robust photostability, efficient reactive oxygen species generation (49%), and excellent photothermal conversion efficiency of about 37.6% under 808 nm laser irradiation. BSS-Et NPs possessed passive tumor-targeting properties in vivo to not only visualize the tumor by NIR fluorescence imaging but also eliminate the tumor without any recurrence by PDT and PTT synergistic therapy under laser irradiation. In addition, benefitting from the characteristics of organic small molecules, they can be metabolized quickly through the liver without inducing toxicity in the whole body. In general, this study provides a new direction for the development of multifunctional phototherapy agents for cancer treatment. This article is protected by copyright. All rights reserved.