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  3. Lipiodol emulsion as a dual chemoradiation-sensitizer for pancreatic cancer treatment

Lipiodol emulsion as a dual chemoradiation-sensitizer for pancreatic cancer treatment

  • J Control Release. 2024 Oct:374:242-253. doi: 10.1016/j.jconrel.2024.08.020.
Shuang Zhu 1,  Chenglu Gu 2,  Long Gao 3,  Shuanglong Du 2,  Duiping Feng 3,  Zhanjun Gu 4
Affiliations

Affiliations

  • 1 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; Spallation Neutron Source Science Center, Institute of High Energy Physics, Dongguan 523803, China.
  • 2 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; Center of Materials Science and Optoelectronics Engineering, College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3 Shanxi Provincial Clinical Research Center for Interventional Medicine, First Hospital of Shanxi Medical University, Taiyuan 030001, China; Department of Oncological and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan 030001, China.
  • 4 CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China; Center of Materials Science and Optoelectronics Engineering, College of Materials Science and Optoelectronic Technology, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: zjgu@ihep.ac.cn.
PMID: 39153723 DOI: 10.1016/j.jconrel.2024.08.020
Abstract

Pancreatic ductal adenocarcinoma (PDAC) has a low survival rate and limited treatment options. Concurrent chemoradiotherapy is considered beneficial to improve tumor control, but the low drug bioavailability at tumor site and the low radiation tolerance of surrounding healthy organs greatly limits its effectiveness. Lipiodol, a natural drug carrier used in clinical transarterial chemoembolization, has shown potential as a radiosensitizer due to its high Z element iodine composition. Thus, this study aims to repurpose lipiodol as a sensitizer to simultaneously enhance chemo- and radiotherapy for PDAC. To this end, a stable lipiodol emulsion (IOE) loaded with gemcitabine is designed using clinically approved Surfactants. At in vivo level, IOE demonstrates better radiotherapeutic effect than existing nanoradiosensitizers and enhanced drug bioavailability over free drug, leading to significant tumor inhibition and improved survival rates under concurrent chemo-radiotherapy. This may due to the sustained drug release, homogenous spatial distribution, and long-term retention ability of IOE in solid PDAC tumor. Furthermore, to better understand the functioning mechanism of drug-loaded IOE, in vitro study is conducted to reveal the ROS- and DNA damage-related therapeutic pathways. Lastly, a comprehensive toxicity assessment also proves the good biocompatibility and safety of as-prepared IOE. This study offers a clinically feasible sensitizer for simultaneous chemoradiotherapy and holds potential for other types of Cancer treatment in clinics.

Keywords

Concurrent chemoradiotherapy; Drug carrier; Lipiodol emulsion; Pancreatic cancer; Radiosensitizer.

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