Iodinated cyanine dye-based nanosystem for synergistic phototherapy and hypoxia-activated bioreductive therapy

• Published in: Drug delivery Vol. 29; no. 1; pp. 238 - 253
• Main Authors: Dong, Yunxia, Zhou, Ling, Shen, Zijun, Ma, Qingming, Zhao, Yifan, Sun, Yong, Cao, Jie
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2022; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Cancer therapies; Cell Survival - drug effects; Chemistry, Pharmaceutical; Chemotherapy; Chromosome Aberrations - drug effects; DNA Damage - drug effects; Drug Carriers - chemistry; Drug Liberation; Hypoxia; Hypoxia - pathology; hypoxia-activated chemotherapy; immune response; iodinated-cyanine dyes; Light therapy; Liposomes - chemistry; Mice; Mice, Inbred BALB C; Nanoparticle Drug Delivery System - chemistry; Particle Size; Photodynamic therapy; Photosensitizing Agents - administration & dosage; Photosensitizing Agents - pharmacokinetics; Photosensitizing Agents - pharmacology; Phototherapy - methods; Reactive Oxygen Species - metabolism; Surface Properties; Tirapazamine - administration & dosage; Tirapazamine - pharmacokinetics; Tirapazamine - pharmacology; Xenograft Model Antitumor Assays; Photodynamic therapy; iodinated-cyanine dyes; immune response; hypoxia-activated chemotherapy
• ISSN: 1071-7544; 1521-0464
• DOI: 10.1080/10717544.2021.2023701

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROS) to kill cancer cells. However, the effectiveness of PDT is greatly reduced due to local hypoxia. Hypoxic activated chemotherapy combined with PDT is expected to be a novel strategy to enhance anti-cancer therapy. Herein, a novel liposome (LCT) incorporated with photosensitizer (PS) and bioreductive prodrugs was developed for PDT-activated chemotherapy. In the design, CyI, an iodinated cyanine dye, which could simultaneously generate enhanced ROS and heat than other commonly used cyanine dyes, was loaded into the lipid bilayer; while tirapazamine (TPZ), a hypoxia-activated prodrug was encapsulated in the hydrophilic nucleus. Upon appropriate near-infrared (NIR) irradiation, CyI could simultaneously produce ROS and heat for synergistic PDT and photothermal therapy (PTT), as well as provide fluorescence signals for precise real-time imaging. Meanwhile, the continuous consumption of oxygen would result in a hypoxia microenvironment, further activating TPZ free radicals for chemotherapy, which could induce DNA double-strand breakage and chromosome aberration. Moreover, the prepared LCT could stimulate acute immune response through PDT activation, leading to synergistic PDT/PTT/chemo/immunotherapy to kill cancer cells and reduce tumor metastasis. Both in vitro and in vivo results demonstrated improved anticancer efficacy of LCT compared with traditional PDT or chemotherapy. It is expected that these iodinated cyanine dyes-based liposomes will provide a powerful and versatile theranostic strategy for tumor target phototherapy and PDT-induced chemotherapy.