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  3. Cell membrane-camouflaged bufalin targets NOD2 and overcomes multidrug resistance in pancreatic cancer

Cell membrane-camouflaged bufalin targets NOD2 and overcomes multidrug resistance in pancreatic cancer

  • Drug Resist Updat. 2023 Nov:71:101005. doi: 10.1016/j.drup.2023.101005.
Wei Zhang 1,  Yibao Fan 2,  Jinze Zhang 3,  Dan Shi 3,  Jiahui Yuan 3,  Milad Ashrafizadeh 3,  Wei Li 4,  Man Hu 5,  A M Abd El-Aty 6,  Ahmet Hacimuftuoglu 7,  Michael Linnebacher 8,  Yongxian Cheng 9,  Weiguang Li 10,  Shuo Fang 11,  Peng Gong 12,  Xianbin Zhang 13
Affiliations

Affiliations

  • 1 Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518055, China; Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, Guangdong 518060, China; International Association for Diagnosis and Treatment of Cancer, Shenzhen, Guangdong 518055, China.
  • 2 Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518055, China; School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518060, China.
  • 3 Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518055, China.
  • 4 College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250000, China.
  • 5 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250000, China.
  • 6 Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, 12211 Giza, Egypt; Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum 25070, Turkey.
  • 7 Department of Medical Pharmacology, Medical Faculty, Ataturk University, Erzurum 25070, Turkey.
  • 8 Clinic of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, Rostock 18059, Germany.
  • 9 School of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong 518060, China.
  • 10 Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, 999077, China. Electronic address: [email protected].
  • 11 Department of Oncology, The Seventh Affiliated Hospital Sun Yat-sen University, Shenzhen, Guangdong 518107, China. Electronic address: [email protected].
  • 12 Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518055, China; International Association for Diagnosis and Treatment of Cancer, Shenzhen, Guangdong 518055, China. Electronic address: [email protected].
  • 13 Department of General Surgery and Institute of Precision Diagnosis and Treatment of Digestive System Tumors, Carson International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, Guangdong 518055, China; International Association for Diagnosis and Treatment of Cancer, Shenzhen, Guangdong 518055, China. Electronic address: [email protected].
PMID: 37647746 DOI: 10.1016/j.drup.2023.101005
Abstract

Aims: Multidrug resistance in pancreatic Cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) and assess its potential to counter chemoresistance in pancreatic Cancer.

Methods: The toxicity of CBAP was evaluated by electrocardiogram, body weight, distress score, and nesting behavior of mice. In addition, the anticarcinoma activity and underlying mechanism were investigated both in vitro and in vivo.

Results: CBAP significantly mitigated BA-mediated acute cardiotoxicity and enhanced the sensitivity of pancreatic Cancer to several clinical drugs, such as gemcitabine, 5-fluorouracil, and FOLFIRINOX. Mechanistically, CBAP directly bound to nucleotide-binding and oligomerization domain containing protein 2 (NOD2) and inhibited the expression of nuclear factor kappa-light-chain-enhancer of activated B cells. This inhibits the expression of ATP-binding cassette transporters, which are responsible for chemoresistance in Cancer cells.

Conclusions: Our findings indicate that CBAP directly inhibits NOD2. Combining CBAP with standard-of-care chemotherapeutics represents a safe and efficient strategy for the treatment of pancreatic Cancer.

Keywords

Bufalin; Cancer cell membrane camouflaging; Multidrug resistance; NOD2; Pancreatic cancer.

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