title: Ring-opening polymerization of prodrugs: a versatile approach to prepare well-defined drug-loaded nanoparticles.
abstract: The synthesis of polymer-drug conjugates from prodrug monomers consisting of a cyclic polymerizable group that is appended to a drug through a cleavable linker is achieved by organocatalyzed ring-opening polymerization. The monomers polymerize into well-defined polymer prodrugs that are designed to self-assemble into nanoparticles and release the drug in response to a physiologically relevant stimulus. This method is compatible with structurally diverse drugs and allows different drugs to be copolymerized with quantitative conversion of the monomers. The drug loading can be controlled by adjusting the monomer(s)/initiator feed ratio and drug release can be encoded into the polymer by the choice of linker. Initiating these monomers from a poly(ethylene glycol) macroinitiator results in amphiphilic diblock copolymers that spontaneously self-assemble into micelles with a long plasma circulation, which is useful for systemic therapy.
authors.affiliation: Department of Biomedical Engineering, Center for Biologically Inspired Materials and Material Systems, Duke University, Durham, NC 27708 (USA).
authors.forename: Jinyao
authors.initials: J
authors.lastname: Liu
authors.forename: Wenge
authors.initials: W
authors.lastname: Liu
authors.forename: Isaac
authors.initials: I
authors.lastname: Weitzhandler
authors.forename: Jayanta
authors.initials: J
authors.lastname: Bhattacharyya
authors.forename: Xinghai
authors.initials: X
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Qi
authors.forename: Somnath
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000633:toxicity; D002166:Camptothecin / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002699:Chlorambucil / Q000737:chemistry / Q000633:toxicity; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D058105:Polymerization; D011355:Prodrugs / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011355:Prodrugs; D002699:Chlorambucil; D011092:Polyethylene Glycols; D002166:Camptothecin
keywords: cancer therapy; nanoparticles; polymer-drug conjugates; polymerizable prodrugs; ring-opening polymerization