title: Polymer-Doxorubicin Conjugate Micelles Based on Poly(ethylene glycol) and Poly(N-(2-hydroxypropyl) methacrylamide): Effect of Negative Charge and Molecular Weight on Biodistribution and Blood Clearance.
abstract: Well-defined water-soluble block copolymers poly(ethylene glycol)-b-poly(N-(2-hydroxypropyl) methacrylamide-co-N-methacryloylglycylglycine) (PEG-b-P(HPMA-co-MAGG)) and their doxorubicin (Dox) conjugates with different composition and molecular weight were synthesized. These Dox conjugates can form micelles in buffer solution. The physicochemical properties, in vivo biodistribution, blood clearance, and especially the tumor accumulation of copolymers and micelles were studied. Severe liver accumulation can be observed for PEG-b-PMAGG copolymers. This was quite different from their Dox conjugate for which decreased RES uptake and elevated kidney accumulation could be observed. When decrease the negative charge to an appropriate amount such as 8-10 mol %, both RES uptake and kidney accumulation could be suppressed. Obvious tumor accumulation could be achieved especially when the molecular weight were increased from ∼40 to ∼80 KDa. These results provided us with a guideline for the design of nanoscaled drug delivery system as well as a potential option for treating kidney-related cancers.
authors.affiliation: The State Key laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology , Beijing 100029, China.
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Yu
authors.affiliation: The CAS Key Laboratory of Engineering Plastics, Institute of Chemistry, Chinese Academy of Sciences (CAS) , Beijing 100190, China.
authors.forename: Zhenke
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Medical Isotopes Research Center, Peking University , Beijing 100191, China.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Shi
authors.affiliation: The State Key laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology , Beijing 100029, China.
authors.forename: Shuli
authors.initials: S
authors.lastname: Guan
authors.affiliation: The State Key laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology , Beijing 100029, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Du
authors.affiliation: The State Key laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology , Beijing 100029, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Shen
authors.affiliation: The State Key laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology , Beijing 100029, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Medical Isotopes Research Center, Peking University , Beijing 100191, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Jia
authors.affiliation: Medical Isotopes Research Center, Peking University , Beijing 100191, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: The State Key laboratory of Organic-inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology , Beijing 100029, China.|The CAS Key Laboratory of Engineering Plastics, Institute of Chemistry, Chinese Academy of Sciences (CAS) , Beijing 100190, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Gan
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D008823:Micelles; D011109:Polymethacrylic Acids; D011092:Polyethylene Glycols; C011533:Duxon; D004317:Doxorubicin; C000595209:polyethylene glycol 1000