title: Molecularly precise dendrimer-drug conjugates with tunable drug release for cancer therapy.
abstract: The structural preciseness of dendrimers makes them perfect drug delivery carriers, particularly in the form of dendrimer-drug conjugates. Current dendrimer-drug conjugates are synthesized by anchoring drug and functional moieties onto the dendrimer peripheral surface. However, functional groups exhibiting the same reactivity make it impossible to precisely control the number and the position of the functional groups and drug molecules anchored to the dendrimer surface. This structural heterogeneity causes variable pharmacokinetics, preventing such conjugates to be translational. Furthermore, the highly hydrophobic drug molecules anchored on the dendrimer periphery can interact with blood components and alter the pharmacokinetic behavior. To address these problems, we herein report molecularly precise dendrimer-drug conjugates with drug moieties buried inside the dendrimers. Surprisingly, the drug release rates of these conjugates were tailorable by the dendrimer generation, surface chemistry, and acidity.
authors.affiliation: Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, 82071 (USA).
authors.forename: Zhuxian
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xinpeng
authors.initials: X
authors.lastname: Ma
authors.forename: Caitlin J
authors.initials: CJ
authors.lastname: Murphy
authors.forename: Erlei
authors.initials: E
authors.lastname: Jin
authors.forename: Qihang
authors.initials: Q
authors.lastname: Sun
authors.forename: Youqing
authors.initials: Y
authors.lastname: Shen
authors.forename: Edward A
authors.initials: EA
authors.lastname: Van Kirk
authors.forename: William J
authors.initials: WJ
authors.lastname: Murdoch
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D002166:Camptothecin / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy; D011107:Polylysine / Q000737:chemistry; D014183:Transplantation, Heterologous
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D002232:Carbocyanines; D050091:Dendrimers; D004337:Drug Carriers; C085321:cyanine dye 5; D011107:Polylysine; D002166:Camptothecin
keywords: camptothecin; dendrimers; drug delivery; drug release; prodrugs