title: ROS-induced nanotherapeutic approach for ovarian cancer treatment based on the combinatorial effect of photodynamic therapy and DJ-1 gene suppression.
abstract: This study represents a novel approach for intraoperative ovarian cancer treatment based on the combinatorial effect of a targeted photodynamic therapy (PDT) associated with suppression of the DJ-1 protein, one of the key players in the ROS defense of cancer cells. To assess the potential of the developed therapy, dendrimer-based nanoplatforms for cancer-targeted delivery of near-infrared photosensitizer, phthalocyanine, and DJ-1 siRNA have been constructed. In vitro studies revealed that therapeutic efficacy of the combinatorial approach was enhanced when compared to PDT alone and this enhancement was more pronounced in ovarian carcinoma cells, which are characterized by higher basal levels of DJ-1 protein. Moreover, the ovarian cancer tumors exposed to a single dose of combinatorial therapy were completely eradicated from the mice and the treated animals showed no evidence of cancer recurrence. Thus, the developed therapeutic approach can be potentially employed intraoperatively to eradicate unresactable cancer cells.
  
  
  BACKGROUND
  The complete clearance of microscopic residual tumor cells during excision surgery is important to improve survival of the patient. In this interesting paper, the authors developed a novel approach using targeted photodynamic therapy (PDT), combining a photosensitizer, phthalocyanine, and DJ-1 siRNA for the treatment of ovarian cancer. The data showed that this approach increased cancer cell killing and may pave way for future clinical studies.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Canan
authors.initials: C
authors.lastname: Schumann
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Olena
authors.initials: O
authors.lastname: Taratula
authors.affiliation: Department of Biochemistry and Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE, USA.
authors.forename: Oleh
authors.initials: O
authors.lastname: Khalimonchuk
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, Oregon State University, Corvallis, OR, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Palmer
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Cronk
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Carson V
authors.initials: CV
authors.lastname: Jones
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA.
authors.forename: Cesar A
authors.initials: CA
authors.lastname: Escalante
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA. Electronic address: Oleh.Taratula@oregonstate.edu.
authors.forename: Oleh
authors.initials: O
authors.lastname: Taratula
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D054833:Isoindoles; D051379:Mice; D008819:Mice, Nude; D049329:Nanostructures / Q000737:chemistry; D015513:Oncogene Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010053:Ovary / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000071617:Protein Deglycase DJ-1; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000627:therapeutic use*; D000067492:RNAi Therapeutics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D050091:Dendrimers; D004337:Drug Carriers; D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D054833:Isoindoles; D015513:Oncogene Proteins; D017319:Photosensitizing Agents; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; C013647:phthalocyanine
keywords: DJ-1; Ovarian cancer; Photodynamic therapy; ROS; siRNA therapy