title: A magnetic vehicle realized tumor cell-targeted radiotherapy using low-dose radiation.
abstract: Radiotherapy, a common cancer treatment, often adversely affects the surrounding healthy tissue and/or cells. Some tumor tissue-focused radiation therapies have been developed to lower radiation-induced lesion formation; however, achieving tumor cell-targeted radiotherapy (i.e., precisely focusing the radiation efficacy to tumor cells) remains a challenge. In the present study, we developed a novel tumor cell-targeted radiotherapy, named targeted sensitization-enhanced radiotherapy (TSER), that exploits tumor-specific folic acid-conjugated carboxymethyl lauryl chitosan/superparamagnetic iron oxide (FA-CLC/SPIO) micelles to effectively deliver chlorin e6 (Ce6, a sonosensitizer) to mitochondria of HeLa cells under magnetic guidance. For the in vitro tests, the sensitization of Ce6 induced by ultrasound, that could weaken the radiation resistant ability of tumor cells, occurred only in Ce6-internalizing tumor cells. Therefore, low-dose X-ray irradiation, that was not harmful to normal cells, could exert high tumor cell-specific killing ability. The ratio of viable normal cells to tumor cells was increased considerably, from 7.8 (at 24h) to 97.1 (at 72h), after they had received TSER treatment. Our data suggest that TSER treatment significantly weakens tumor cells, resulting in decreased viability in vitro as well as decreased in vivo subcutaneous tumor growth in nude mice, while the adverse effects were minimal. Taken together, TSER treatment appears to be an effective, clinically feasible tumor cell-targeted radiotherapy that can solve the problems of traditional radiotherapy and photodynamic therapy.
authors.affiliation: Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Hsiao-Ping
authors.initials: HP
authors.lastname: Chen
authors.affiliation: Department of Orthopaedic Surgery, Taipei City Hospital, Taipei, Taiwan, ROC.
authors.forename: Fu-I
authors.initials: FI
authors.lastname: Tung
authors.affiliation: Division of Neurosurgery, Department of Surgery, Cathay General Hospital, Taipei, Taiwan, ROC; School of Medicine, Fu Jen Catholic University, Taipei, Taiwan, ROC.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, Taiwan, ROC. Electronic address: andyliudpum@yahoo.com.tw.
authors.forename: Tse-Ying
authors.initials: TY
authors.lastname: Liu
mesh_terms: D000818:Animals; D048271:Chitosan / Q000031:analogs & derivatives* / Q000737:chemistry; D002735:Chlorophyllides; D016503:Drug Delivery Systems; D005260:Female; D005290:Ferric Compounds / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D059346:Magnets / Q000737:chemistry*; D008819:Mice, Nude; D008823:Micelles; D009369:Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011166:Porphyrins / Q000008:administration & dosage* / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D002735:Chlorophyllides; D005290:Ferric Compounds; D008823:Micelles; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C514968:carboxymethyl-chitosan; C000499:ferric oxide; C062985:phytochlorin; D048271:Chitosan; D005492:Folic Acid
keywords: Chlorin e6; Drug vehicle; Magnetic guidance; Targeted delivery; Tumor cell-targeted radiotherapy