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

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

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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