title: Multistage vector delivery of sulindac and silymarin for prevention of colon cancer.
abstract: Familial adenomatous polyposis (FAP) is an inherited condition secondary to germline mutations in the APC gene, thus resulting in the formation of hundreds of colonic adenomas that eventually progress into colon cancer. Surgical removal of the colon remains the only treatment option to avoid malignancy, as long-term exposure to chemopreventive agents such as sulindac (a non-steroidal anti-inflammatory drug) and silymarin (phytoestrogen) is not feasible. Here, we have developed a multistage silicon-based drug delivery platform for sulindac and silymarin that preferentially interacts with colon cancer cells as opposed to normal intestinal mucosa. Preferential binding and internalization of these drugs into colon cancer cells was obtained using a targeting strategy against the protein meprin A, which we demonstrate is overexpressed in human colon cancer cells and in the small intestine of Apc(Min/+) mice. We propose that this delivery system could potentially be used to reduce drug-induced side effects in FAP patients, thus enabling long-term prevention of adenoma formation.
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: mpsc227@uky.edu.
authors.forename: Maria Principia
authors.initials: MP
authors.lastname: Scavo
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Thoracic & Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Gentile
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; CAS Key Laboratory for Biomedical Effects of Nanomaterials & Nanosafety, National Center for Nanoscience & Technology of China, Beijing 100190, China.
authors.forename: Joy
authors.initials: J
authors.lastname: Wolfram
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Gu
authors.affiliation: Gastroentrology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari 70121, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Barone
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Evangelopoulos
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Jonathan O
authors.initials: JO
authors.lastname: Martinez
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pharmacy, University G. d'Annunzio of Chieti, Pescara 66013, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Celia
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Ennio
authors.initials: E
authors.lastname: Tasciotti
authors.affiliation: Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Vilar
authors.affiliation: Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030, USA; Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Haifa
authors.initials: H
authors.lastname: Shen
mesh_terms: D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000517:prevention & control*; D006801:Humans; D012838:Silymarin / Q000008:administration & dosage*; D013467:Sulindac / Q000008:administration & dosage*
chemical_list: D016588:Anticarcinogenic Agents; D012838:Silymarin; D013467:Sulindac
keywords: Colon cancer; Drug delivery; FAP; Multistage vector; Silymarin; Sulindac