title: A highly tumor-specific light-triggerable drug carrier responds to hypoxic tumor conditions for effective tumor treatment.
abstract: Light-triggered drug delivery is among the most investigated stimulus-response strategies and has been widely explored in cancer treatment. However, the limited specificity of light-triggered drug delivery reduces the therapeutic efficacy and causes considerable undesirable side effects. In this work, we demonstrate a highly tumor-specific light-triggerable drug carrier (H-LTDC) induced by a combination of internal (i.e., tumor hypoxia) and external stimuli (i.e., light). The doxorubicin (DOX)-loaded H-LTDC was self-assembled from type-1-reactive oxygen species (ROStype1)-mediated degradable chondroitin sulfate (CS) conjugated with a photosensitizer (PS), Pheophorbide-a, which has a spherical shape and a uniform size distribution. Under hypoxic conditions, ROSType1 was mainly generated due to the electron-rich sulfate groups in the polysaccharide backbone. The ROStype1 generated by H-LTDC allowed laser-triggered drug release at low oxygen concentrations. From the in vitro cytotoxicity tests with colon cancer cells (HCT-116), under laser irradiation, DOX-loaded H-LTDCs showed higher toxicity under hypoxic conditions than that under normoxic conditions. In vivo and ex vivo biodistribution studies demonstrated that H-LTDCs selectively accumulated in the tumor tissues. As a result, drug-loaded H-LTDCs exhibited high anti-tumor activity in vivo. Overall, we believe that this approach could represent a promising platform for the treatment of tumor and hypoxia-associated diseases without undesirable side effects.
authors.affiliation: Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, 43 Jibongro, Wonmi-gu, Bucheon-si, Gyeonggi do, 14662, Republic of Korea.
authors.forename: Wooram
authors.initials: W
authors.lastname: Park
authors.affiliation: Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, 43 Jibongro, Wonmi-gu, Bucheon-si, Gyeonggi do, 14662, Republic of Korea.
authors.forename: Byoung-chan
authors.initials: BC
authors.lastname: Bae
authors.affiliation: Center for Photomedicine, Department of Biotechnology, The Catholic University of Korea, 43 Jibongro, Wonmi-gu, Bucheon-si, Gyeonggi do, 14662, Republic of Korea. Electronic address: kna6997@catholic.ac.kr.
authors.forename: Kun
authors.initials: K
authors.lastname: Na
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D002236:Carbohydrate Conformation; D015687:Cell Hypoxia; D002734:Chlorophyll / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000528:radiation effects; D002809:Chondroitin Sulfates / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers / Q000528:radiation effects; D016503:Drug Delivery Systems; D004735:Energy Transfer; D045325:HCT116 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D054023:Lasers, Semiconductor; D008027:Light; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000528:radiation effects; D055100:Optical Fibers; D010084:Oxidation-Reduction; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage* / Q000528:radiation effects; D011134:Polysaccharides / Q000737:chemistry; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology; D026082:Singlet Oxygen; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D017319:Photosensitizing Agents; D011134:Polysaccharides; D017382:Reactive Oxygen Species; D002734:Chlorophyll; D026082:Singlet Oxygen; D004317:Doxorubicin; D006820:Hyaluronic Acid; D002809:Chondroitin Sulfates; C032623:pheophorbide a
keywords: Drug delivery; Light-triggered; Photosensitizer; Tumor hypoxia; Tumor treatment