Title: | Theranostic Liposomes with Hypoxia-Activated Prodrug to Effectively Destruct Hypoxic Tumors Post-Photodynamic Therapy |
Authors: | Liangzhu Feng,†,‡Liang Cheng,†,§Ziliang Dong,†Danlei Tao,†Todd E. Barnhart,§ WeiboCai,*,§ Meiwan Chen,*,‡ and Zhuang Liu*,† |
†Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China ‡State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China §Departments of Radiology and Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States | |
Abstract: | Photodynamic therapy (PDT), a noninvasivecancer therapeutic method triggered by light, would lead tosevere tumor hypoxia after treatment. Utilizing a hypoxiaactivated prodrug, AQ4N, which only shows toxicity to cancercells under hypoxic environment, herein, a multipurposeliposome is prepared by encapsulating hydrophilic AQ4N and hydrophobic hexadecylamine conjugated chlorin e6 (hCe6), aphotosensitizer, into its aqueous cavity and hydrophobicbilayer, respectively. After chelating a 64Cu isotope with Ce6, the obtained AQ4N-64Cu-hCe6-liposome is demonstrated tobe an effective imaging probe for in vivo positron emissiontomography, which together with in vivo fluorescence and photoacoustic imaging uncovers efficient passive homing ofthose liposomes after intravenous injection. After being irradiated with the 660 nm light-emitting diode light, the tumorbearing mice with injection of AQ4N-hCe6-liposome show severe tumor hypoxia, which in turn would trigger activation of AQ4N, and finally contributes to remarkably improved cancer treatment outcomes via sequential PDT and hypoxiaactivated chemotherapy. This work highlights a liposome-based theranostic nanomedicine that could utilize tumor hypoxia,a side effect of PDT, to trigger chemotherapy, resulting in greatly improved efficacy compared to conventional cancer PDT. |
IF: | 13.334 |
Link: | http://pubs.acs.org/doi/abs/10.1021/acsnano.6b07525 Editor: Danting Xiang |