Combined Cancer Chemo-Photodynamic and Photothermal Therapy Based on ICG/PDA/TPZ-Loaded Nanoparticles.

Abstract

Although photodynamic therapy (PDT) has been an attractive strategy for several cancer treatments in the clinical setting, PDT efficacy is attenuated by consumption of oxygen. To address this photodynamic issue, we adopted a phototherapy-chemotherapy combination strategy based on targeted delivery of the near-infrared photosensitizer indocyanine green (ICG), photothermal conversion agent polydopamine (PDA), and tirapazamine (TPZ), a hypoxia-activated prodrug. Under laser irradiation, ICG consumption of oxygen and aggravated hypoxia in tumor sites can activate TPZ to damage DNA. In parallel, ICG produces reactive oxygen species which work in synergy with PDA to enhance phototherapeutic efficiency. Herein, hybrid CaCO3/TPGS nanoparticles delivering ICG, PDA, and TPZ (ICG-PDA-TPZ NPs) were designed for effective and safe cancer therapy. ICG-PDA-TPZ NPs showed significantly improved cellular uptake and accumulation in tumors. Furthermore, we demonstrated that ICG-PDA-TPZ NPs showed intensive photodynamic and photothermal effects in vitro and in vivo, which synergized with TPZ in subcutaneous U87 malignant glioma growth and orthotopic B16F10 tumor inhibition, with negligible side effects. Thus, ICG-PDA-TPZ NPs could be an effective strategy for improvement of PDT.

• Authors: Xiaqin Huang, Junru Wu, Muye He, Xinyu Hou, Yan Wang, Xiaoran Cai, Hongliang Xin, Feng Gao, Yanzuo Chen
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 16 Issue 5 Pg. 2172-2183 (05 06 2019) ISSN: 1543-8392 [Electronic] United States
• PMID: 30978027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indocyanine Green
• Indoles
• polydopamine
• Polymers
• Prodrugs
• Radiation-Sensitizing Agents
• Reactive Oxygen Species
• Tirapazamine

Topics

• Animals
• Humans
• Mice
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Delivery Systems
• Hyperthermia, Induced (methods)
• Indocyanine Green (metabolism, therapeutic use)
• Indoles (metabolism, therapeutic use)
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Nude
• Nanoparticles
• Neoplasms (drug therapy)
• Photochemotherapy (adverse effects, methods)
• Polymers (metabolism, therapeutic use)
• Prodrugs (metabolism, therapeutic use)
• Radiation-Sensitizing Agents (metabolism, therapeutic use)
• Reactive Oxygen Species (radiation effects)
• Tirapazamine (metabolism, therapeutic use)
• Tissue Distribution
• Treatment Outcome
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays