Chlorin e6 Conjugated Poly(dopamine) Nanospheres as PDT/PTT Dual-Modal Therapeutic Agents for Enhanced Cancer Therapy

                Chlorin e6 Conjugated Poly(dopamine) Nanospheres as PDT/PTT Dual-Modal Therapeutic Agents for Enhanced Cancer Therapy

Da Zhang^†‡, Ming Wu^†‡, Yongyi Zeng^†‡§, Lingjie Wu^†‡, Qingtang Wang^†‡, Xiao Han^∥, Xiaolong Liu^*†‡, and Jingfeng Liu^*†‡§

^† The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People’s Republic of China

^‡ The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People’s Republic of China

^§ Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China

^∥ Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, People’s Republic of China

ACS Appl. Mater. Interfaces, 2015, 7 (15), pp 8176–8187

DOI: 10.1021/acsami.5b01027

Publication Date (Web): April 10, 2015

Copyright © 2015 American Chemical Society

*E-mail: xiaoloong.liu@gmail.com (X. Liu)., *E-mail: drjingfeng@126.com (J. Liu).

Abstract

Photodynamic therapy (PDT), using a combination of chemical photosensitizers (PS) and light, has been successfully applied as a noninvasive therapeutic procedure to treat tumors by inducing apoptosis or necrosis of cancer cells. However, most current clinically used PS have suffered from the instability in physiological conditions which lead to low photodynamic therapy efficacy. Herein, a highly biocompatible poly(dopamine) (PDA) nanoparticle conjugated with Chlorin e6 (referenced as the PDA-Ce6 nanosphere) was designed as a nanotherapeutic agent to achieve simultaneous photodynamic/photothermal therapy (PDT/PTT). Compared to the free Ce6, the PDA-Ce6 nanosphere exhibited significantly higher PDT efficacy against tumor cells, because of the enhanced cellular uptake and subsequently greater reactive oxygen species (ROS) production upon laser irradiation at 670 nm. Meanwhile, the PDA-Ce6 nanosphere could be also used as a photoabsorbing agent for PTT, because of the excellent photothermal conversion ability of PDA nanoparticle under laser irradiation at 808 nm. Moreover, our prepared nanosphere had extremely low dark toxicity, while excellent phototoxicity under the combination laser irradiation of 670 and 808 nm, both in vitro and in vivo, compared to any single laser irradiation alone. Therefore, our prepared PDA-Ce6 nanosphere could be applied as a very promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

Keywords:

poly(dopamine) nanoparticles (PDA NPs); Chlorin e6 (Ce6); photodynamic therapy (PDT); photothermal therapy (PTT); cancer therapy