title: Redox-responsive polycation-functionalized cotton cellulose nanocrystals for effective cancer treatment.
abstract: Carbon nanotubes have excellent penetrability and encapsulation efficiency in the fields of drug and gene delivery. Because of their excellent physicochemical properties, biocompatible rodlike cellulose nanocrystals (CNCs) were reportedly expected to replace carbon nanotubes. In this work, CNCs from natural cotton wool were functionalized with disulfide bond-linked poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes for effective biomedical applications. A range of CNC-graft-PDMAEMA vectors (termed as CNC-SS-PDs) with various molecular weights of PDMAEMA were synthesized. Under reducible conditions, PDMAEMA chains can be easily cleaved from CNCs. The gene condensation ability, reduction sensitivity, cytotoxicity, gene transfection, and in vivo antitumor activities of CNC-SS-PDs were investigated in detail. The CNC-SS-PDs exhibited good transfection efficiencies and low cytotoxicities. The needlelike shape of CNCs had an important effect on enhancing transfection efficiency. The antitumor effect of CNC-SS-PDs was evaluated by a suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine, CD/5-FC) in vitro and in vivo. This research demonstrates that the functionalization of CNCs with redox-responsive polycations is an effective method for developing novel gene delivery systems.
authors.affiliation: ‡Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029, China.|§Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: ∥State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: ⊥Brain Tumor Research Center, Beijing Neurosurgical Institute, Beijing Tiantan Hospital affiliated with Capital Medical University, Beijing 100050, China.
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Liu
authors.affiliation: #Department of Chemical and Biomolecular Engineering, University of Akron, Akron, Ohio 44325, United States.
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.affiliation: ‡Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029, China.|§Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, China.
authors.forename: Fu-Jian
authors.initials: FJ
authors.lastname: Xu
authors.affiliation: ∥State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Beijing 100021, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019556:COS Cells; D002470:Cell Survival / Q000187:drug effects; D002482:Cellulose / Q000737:chemistry*; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D003368:Gossypium / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008689:Methacrylates / Q000737:chemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000628:therapy*; D009757:Nylons / Q000737:chemistry; D010084:Oxidation-Reduction / Q000187:drug effects; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry*; D000071228:Polyelectrolytes; D058105:Polymerization; D055672:Static Electricity; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D002482:Cellulose; D004247:DNA; D008156:Luciferases; D008689:Methacrylates; D009757:Nylons; D011073:Polyamines; D000071228:Polyelectrolytes; C407037:poly(2-(dimethylamino)ethyl methacrylate)
keywords: ATRP; PDMAEMA; antitumor; bioreducible; cellulose; gene transfection