title: Nano-Fenton Reactors as a New Class of Oxidative Stress Amplifying Anticancer Therapeutic Agents.
abstract: Cancer cells, compared to normal cells, are under oxidative stress associated with an elevated level of reactive oxygen species (ROS) and are more vulnerable to oxidative stress induced by ROS generating agents. Thus, manipulation of the ROS level provides a logical approach to kill cancer cells preferentially, without significant toxicity to normal cells, and great efforts have been dedicated to the development of strategies to induce cytotoxic oxidative stress for cancer treatment. Fenton reaction is an important biological reaction in which irons convert hydrogen peroxide (H2O2) to highly toxic hydroxyl radicals that escalate ROS stress. Here, we report Fenton reaction-performing polymer (PolyCAFe) micelles as a new class of ROS-manipulating anticancer therapeutic agents. Amphiphilic PolyCAFe incorporates H2O2-generating benzoyloxycinnamaldehyde and iron-containing compounds in its backbone and self-assembles to form micelles that serve as Nano-Fenton reactors to generate cytotoxic hydroxyl radicals, killing cancer cells preferentially. When intravenously injected, PolyCAFe micelles could accumulate in tumors preferentially to remarkably suppress tumor growth, without toxicity to normal tissues. This study demonstrates the tremendous translatable potential of Nano-Fenton reactors as a new class of anticancer drugs.
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University , Jeonju, Chonbuk 561-756, Republic of Korea.
authors.forename: Byeongsu
authors.initials: B
authors.lastname: Kwon
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University , Jeonju, Chonbuk 561-756, Republic of Korea.
authors.forename: Eunji
authors.initials: E
authors.lastname: Han
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University , Jeonju, Chonbuk 561-756, Republic of Korea.
authors.forename: Wonseok
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University , Jeonju, Chonbuk 561-756, Republic of Korea.
authors.forename: Wooram
authors.initials: W
authors.lastname: Cho
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University , Jeonju, Chonbuk 561-756, Republic of Korea.
authors.forename: Wooyoung
authors.initials: W
authors.lastname: Yoo
authors.affiliation: Carbon Convergence Materials Research Center, Korea Institute of Science and Technology , Wanju, Chonbuk 565-905, Republic of Korea.
authors.forename: Junyeon
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Laboratory of Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology , Daejeon, 305-806, Republic of Korea.
authors.forename: Byoung-Mog
authors.initials: BM
authors.lastname: Kwon
authors.affiliation: Department of BIN Convergence Technology, Chonbuk National University , Jeonju, Chonbuk 561-756, Republic of Korea.|Department of Polymer-Nano Science and Technology, Chonbuk National University , Jeonju, Chonbuk 561-756, Republic of Korea.
authors.forename: Dongwon
authors.initials: D
authors.lastname: Lee
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D005296:Ferrous Compounds / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000737:chemistry / Q000494:pharmacology; D007501:Iron / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D000075163:Metallocenes; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D041681:NIH 3T3 Cells; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; C045076:Fenton's reagent; D005296:Ferrous Compounds; D000075163:Metallocenes; D008823:Micelles; D011108:Polymers; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron; C004998:ferrocene
keywords: Fenton reaction; cancer; hydroxyl radical; oxidative stress; polymeric micelles