Study on tumour cell-derived hybrid exosomes as dasatinib nanocarriers for pancreatic cancer therapy

  • Artif Cells Nanomed Biotechnol. 2023 Dec;51(1):532-546. doi: 10.1080/21691401.2023.2264358.
Xiaofei Zhou  1  2 ,  Yuetang Zhuang  1 ,  Xiaohong Liu  3 ,  Yaowen Gu  4  5 ,  Junting Wang  6 ,  Yuchen Shi  7 ,  Li Zhang  1 ,  Rui Li  1 ,  Yelin Zhao  1 ,  Hebing Chen  6 ,  Jiao Li  4 ,  Hongjuan Yao  1 ,  Liang Li  1
Affiliations
  • 1. Key Laboratory of Antibiotic Bioengineering of National Health and Family Planning Commission (NHFPC), Institute of Medicinal Biotechnology (IMB), Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China.
  • 2. Department of Clinical Research Center, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China.
  • 3. Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
  • 4. Institute of Medical Information/Library, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 5. Department of Chemistry, NY University, New York City, NY, USA.
  • 6. Beijing Institute of Radiation Medicine, Beijing, China.
  • 7. Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
PMID: 37948136 DOI: 10.1080/21691401.2023.2264358
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death. Therefore, we intend to explore novel strategies against PDAC. The exosomes-based biomimetic nanoparticle is an appealing candidate served as a drug carrier in Cancer treatment, due to its inherit abilities. In the present study, we designed dasatinib-loaded hybrid exosomes by fusing human pancreatic Cancer cells derived exosomes with dasatinib-loaded liposomes, followed by characterization for particle size (119.9 ± 6.10 nm) and zeta potential (-11.45 ± 2.24 mV). Major protein analysis from western blot techniques reveal the presence of exosome marker proteins CD9 and CD81. PEGylated hybrid exosomes showed pH-sensitive drug release in acidic condition, benefiting drug delivery to acidic Cancer environment. Dasatinib-loaded hybrid exosomes exhibited significantly higher uptake rates and cytotoxicity to parent PDAC cells by two-sample t-test or by one-way ANOVA analysis of variance, as compared to free drug or liposomal formulations. The results from our computational analysis demonstrated that the drug-likeness, ADMET, and protein-ligand binding affinity of dasatinib are verified successfully. Cancer derived hybrid exosomes may serve as a potential therapeutic candidate for pancreatic Cancer treatment.

Keywords
Exosomes; dasatinib; hybrid exosomes; liposomes; pancreatic cancer therapy.
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