title: Bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels for targeted X-ray computed tomography imaging and chemotherapy of breast tumors.
abstract: Nanotheranostics is a rapidly growing field combining disease diagnosis and therapy, which ultimately may add in the development of 'personalized medicine'. Here, we designed and developed bioresponsive and fluorescent hyaluronic acid-iodixanol nanogels (HAI-NGs) for targeted X-ray computed tomography (CT) imaging and chemotherapy of MCF-7 human breast tumors. HAI-NGs were obtained with a small size of ca. 90nm, bright green fluoresence and high serum stability from hyaluronic acid-cystamine-tetrazole and reductively degradable polyiodixanol-methacrylate via nanoprecipitation and a photo-click crosslinking reaction. Notably, paclitaxel (PTX)-loaded HAI-NGs showed a fast glutathione-responsive drug release. Confocal microscopy displayed efficient uptake of HAI-NGs by CD44 overexpressing MCF-7 cells via a receptor-mediated mechanism. MTT assays revealed that HAI-NGs were nontoxic to MCF-7 cells even at a high concentration of 1mg/mL whereas PTX-loaded HAI-NGs exhibited strong inhibition of MCF-7 cells. The in vivo pharmcokinetics, near-infrared imaging and biodistribution studies revealed that HAI-NGs significantly prolonged the blood circulation time and enhanced tumor accumulation of PTX. Interestingly, significantly enhanced CT imaging was observed for MCF-7 breast tumors in nude mice via either intratumoral or intravenous injection of HAI-NGs as compared to iodixanol. HAI-NGs fluoresence was distributed thoughout the whole tumor indicating deep tumor penetration. PTX-loaded HAI-NGs showed effective suppression of tumor growth with little systemic toxicity. HAI-NGs appear as a "smart" theranostic nanoplatform for the treatment of CD44 positive tumors.
authors: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced FunctionalPolymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou, 215123, PR China; Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500, AE, Enschede, The Netherlands.
authors: Yaqin
authors: Y
authors: Zhu
authors: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced FunctionalPolymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou, 215123, PR China.
authors: Xiuxiu
authors: X
authors: Wang
authors: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced FunctionalPolymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou, 215123, PR China.
authors: Jing
authors: J
authors: Chen
authors: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced FunctionalPolymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou, 215123, PR China.
authors: Jian
authors: J
authors: Zhang
authors: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced FunctionalPolymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou, 215123, PR China.
authors: Fenghua
authors: F
authors: Meng
authors: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced FunctionalPolymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou, 215123, PR China.
authors: Chao
authors: C
authors: Deng
authors: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced FunctionalPolymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou, 215123, PR China.
authors: Ru
authors: R
authors: Cheng
authors: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced FunctionalPolymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou, 215123, PR China; Department of Polymer Chemistry and Biomaterials, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, P.O. Box 217, 7500, AE, Enschede, The Netherlands. Electronic address: j.feijen@tnw.utwente.nl.
authors: Jan
authors: J
authors: Feijen
authors: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced FunctionalPolymer Design and Application, College of Chemistry, Chemical Engineering and MaterialsScience, Soochow University, Suzhou, 215123, PR China. Electronic address: zyzhong@suda.edu.cn.
authors: Zhiyuan
authors: Z
authors: Zhong
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D065546:Drug Liberation; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D014283:Triiodobenzoic Acids / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D005456:Fluorescent Dyes; D014283:Triiodobenzoic Acids; D006820:Hyaluronic Acid; C044834:iodixanol; D017239:Paclitaxel
keywords: Cancer; Hyaluronic acid; Nanogels; Paclitaxel; Reduction-sensitive; X-ray computed tomography