Complex Structured Fluorescent Polythiophene Graft Copolymer as a Versatile Tool for Imaging, Targeted Delivery of Paclitaxel, and Radiotherapy.
Advances in polymer chemistry resulted in substantial interest to utilize their diverse intrinsic advantages for biomedical research. Especially, studies on drug delivery for tumors have increased to a great extent. In this study, a novel fluorescent graft copolymer has been modified by a drug and targeting moiety and the resulting structure has been characterized by alterations in fluorescent intensity. The polythiophene based hybrid graft copolymer was synthesized by successive organic reactions and combination of in situ N-carboxy anhydride (NCA) ring opening and Suzuki coupling polymerization processes. Initially, targeted delivery of the graft copolymer was investigated by introducing a tumor specific ligand, anti-HER2/neu antibody, on the structure. The functionalized polymer was able to differentially indicate HER2-expressing A549 human lung carcinoma cells, whereas no signal was obtained for Vero, monkey kidney epithelial cells, and HeLa, human cervix adenocarcinoma cells. After integrating paclitaxel into the structure, cell viability, cell cycle progression, and radiosensitivity studies demonstrate HER2/neu targeting polymers were most effective to inhibit cell proliferation. Importantly, the graft copolymer used had no cytotoxic effects to cells, as evidenced by cell viability and cell cycle analysis. This work clearly confirms that a specially designed and fabricated graft copolymer with a highly complex structure is a promising theranostic agent capable of targeting tumor cells for diagnostic and therapeutic purposes.
Ege University , Faculty of Science, Department of Biochemistry, 35100-Bornova, Izmir, Turkey.|Ege University , Institute on Drug Abuse, Toxicology & Pharmaceutical Sciences, 35100-Bornova, Izmir, Turkey.
Emine
E
Guler
Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University , 34467-Istanbul, Turkey.
Huseyin
H
Akbulut
Ege University , Institute on Drug Abuse, Toxicology & Pharmaceutical Sciences, 35100-Bornova, Izmir, Turkey.
Caner
C
Geyik
Ege University , Institute on Drug Abuse, Toxicology & Pharmaceutical Sciences, 35100-Bornova, Izmir, Turkey.
Tulay
T
Yilmaz
Ege University , Institute on Drug Abuse, Toxicology & Pharmaceutical Sciences, 35100-Bornova, Izmir, Turkey.
Z Pinar
ZP
Gumus
Ege University , Faculty of Science, Department of Biochemistry, 35100-Bornova, Izmir, Turkey.
F Baris
FB
Barlas
Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University , 34467-Istanbul, Turkey.
Recep Erdem
RE
Ahan
Ege University , Faculty of Science, Department of Biochemistry, 35100-Bornova, Izmir, Turkey.
Dilek Odaci
DO
Demirkol
Molecular Engineering Institute, Kinki University , 11-6 Kayanomori, Iizuka, Fukuoka 820-8555, Japan.
Shuhei
S
Yamada
Molecular Engineering Institute, Kinki University , 11-6 Kayanomori, Iizuka, Fukuoka 820-8555, Japan.
Takeshi
T
Endo
Ege University , Faculty of Science, Department of Biochemistry, 35100-Bornova, Izmir, Turkey.|Ege University , Institute on Drug Abuse, Toxicology & Pharmaceutical Sciences, 35100-Bornova, Izmir, Turkey.
Suna
S
Timur
Department of Chemistry, Faculty of Science and Letters, Istanbul Technical University , 34467-Istanbul, Turkey.
Yusuf
Y
Yagci
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*; D011836:Radiation Tolerance / Q000187:drug effects*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013876:Thiophenes / Q000737:chemistry*; D014709:Vero Cells
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D017239:Paclitaxel; D011108:Polymers; D018719:Erb-b2 Receptor Tyrosine Kinases; D013876:Thiophenes; C066730:polythiophene; C508053:ERBB2 protein, human