Edible ginger-derived nanoparticles: A novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer.
There is a clinical need for new, more effective treatments for chronic and debilitating inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. In this study, we characterized a specific population of nanoparticles derived from edible ginger (GDNPs 2) and demonstrated their efficient colon targeting following oral administration. GDNPs 2 had an average size of ∼230 nm and exhibited a negative zeta potential. These nanoparticles contained high levels of lipids, a few proteins, ∼125 microRNAs (miRNAs), and large amounts of ginger bioactive constituents (6-gingerol and 6-shogaol). We also demonstrated that GDNPs 2 were mainly taken up by intestinal epithelial cells (IECs) and macrophages, and were nontoxic. Using different mouse colitis models, we showed that GDNPs 2 reduced acute colitis, enhanced intestinal repair, and prevented chronic colitis and colitis-associated cancer (CAC). 2D-DIGE/MS analyses further identified molecular target candidates of GDNPs 2 involved in these mouse models. Oral administration of GDNPs 2 increased the survival and proliferation of IECs and reduced the pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β), and increased the anti-inflammatory cytokines (IL-10 and IL-22) in colitis models, suggesting that GDNPs 2 has the potential to attenuate damaging factors while promoting the healing effect. In conclusion, GDNPs 2, nanoparticles derived from edible ginger, represent a novel, natural delivery mechanism for improving IBD prevention and treatment with an added benefit of overcoming limitations such as potential toxicity and limited production scale that are common with synthetic nanoparticles.
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA. Electronic address: mzhang21@gsu.edu.
Mingzhen
M
Zhang
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Emilie
E
Viennois
Veterans Affairs Medical Center, Decatur, GA, USA; Emory University, Department of Medicine, USA.
Meena
M
Prasad
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Yunchen
Y
Zhang
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; Veterans Affairs Medical Center, Decatur, GA, USA.
Lixin
L
Wang
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Zhan
Z
Zhang
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA.
Moon Kwon
MK
Han
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; Institute for Clean Energy and Advanced Materials, Faculty for Materials and Energy, Southwest University, Chongqing, 400715, PR China.
Bo
B
Xiao
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; The 2nd Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325027, PR China.
Changlong
C
Xu
Veterans Affairs Medical Center, Decatur, GA, USA; Emory University, Department of Medicine, USA.
Shanthi
S
Srinivasan
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30303, USA; Veterans Affairs Medical Center, Decatur, GA, USA.
Didier
D
Merlin
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D002396:Catechols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy* / Q000517:prevention & control; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D020939:Zingiber officinale / Q000737:chemistry; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D008517:Phytotherapy
D000972:Antineoplastic Agents, Phytogenic; D002396:Catechols; D005233:Fatty Alcohols; C040115:shogaol; C007845:gingerol
Colitis-associated cancer; Edible ginger derived nanoparticles; Inflammatory bowel disease; Natural drug delivery system; Therapy