2. Academic Validation
  3. Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations

Construction of gastric cancer patient-derived organoids and their utilization in a comparative study of clinically used paclitaxel nanoformulations

  • J Nanobiotechnology. 2022 May 18;20(1):233. doi: 10.1186/s12951-022-01431-8.
Jiale Zou  # 1 2,  Shuang Wang  # 2,  Ningli Chai  # 1,  Hua Yue 2,  Peng Ye 2,  Peilin Guo 2 3,  Feng Li 2 3,  Bo Wei 4,  Guanghui Ma 5 6,  Wei Wei 7 8,  Enqiang Linghu 9
Affiliations

Affiliations

  • 1 Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
  • 2 State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, People's Republic of China.
  • 3 School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China.
  • 4 Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
  • 5 State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, People's Republic of China. ghma@ipe.ac.cn.
  • 6 School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China. ghma@ipe.ac.cn.
  • 7 State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, People's Republic of China. weiwei@ipe.ac.cn.
  • 8 School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing, 100049, People's Republic of China. weiwei@ipe.ac.cn.
  • 9 Department of Gastroenterology and Hepatology, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People's Republic of China. linghuenqiang@vip.sina.com.
  • # Contributed equally.
PMID: 35585597 DOI: 10.1186/s12951-022-01431-8
Abstract

Background: Gastric Cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal.

Results: Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route.

Conclusions: This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy.

Keywords

Albumin-bound paclitaxel; Gastric cancer; Liposomal paclitaxel; Nanoformulation; Patient-derived organoids.

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