title: Reactive oxygen species responsive drug releasing nanoparticle based on chondroitin sulfate-anthocyanin nanocomplex for efficient tumor therapy.
abstract: To develop a reactive oxygen species (ROS) sensitive drug carrier, a chondroitin sulfate (CS)-anthocyanin (ATC) based nanocomplex was developed. Doxorubicin hydrochloride (DOX) was loaded in the CS-ATC nanocomplex (CS-ATC-DOX) via intermolecular stacking interaction. The nanocomplex was fabricated by a simple mixing method in the aqueous phase. The morphology and size of CS-ATC-DOX were determined by ATC content. In the group with 1.5mg/ml of ATC loaded CS-ATC-DOX (CS-ATC2-DOX), the drug content and loading efficiency were 8.5% and 99.1%, respectively. The ROS sensitive drug release of CS-ATC2-DOX was confirmed under in vitro physiological conditions. The results demonstrated that 1.67 times higher DOX release occurred in CS-ATC2-DOX for 48h compared to CS-DOX (ATC absent sample). Drug release and nanocomplex destruction were induced by ROS mediated ATC degradation. We determined that 66.7% of ROS was scavenged by CS-ATC2-DOX. Additionally, an HCT-116 tumor bearing animal model was used to confirm ROS sensitive therapeutic effects of CS-ATC2-DOX. The results indicate that DOX was released from the intravenously injected CS-ATC2-DOX in the tumor tissue. Thus, nuclei shrinkage and dead cells were observed in H&E staining and TUNEL assay, respectively. These data suggest that the tumor growth was effectively inhibited. This study means that CS-ATC2-DOX has potential in improving tumor therapy.
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, South Korea.
authors.forename: Dooyong
authors.initials: D
authors.lastname: Jeong
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, South Korea.
authors.forename: Byoung-Chan
authors.initials: BC
authors.lastname: Bae
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, South Korea.
authors.forename: Sin-Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, South Korea. Electronic address: kna6997@catholic.ac.kr.
authors.forename: Kun
authors.initials: K
authors.lastname: Na
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002809:Chondroitin Sulfates / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D065546:Drug Liberation; D045325:HCT116 Cells; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism*; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000872:Anthocyanins; D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D002809:Chondroitin Sulfates
keywords: Anthocyanin; Chondroitin sulfate; Doxorubicin; Reactive oxygen species; Tumor therapy