Fentanyl Initiated Polymers Prepared by ATRP for Targeted Delivery.
The targeted delivery of polymers to neurons is a challenging yet important goal for polymer based drug delivery. We prepared a fentanyl based atom transfer radical polymerization (ATRP) initiator to target the Mu opioid receptor (MOR) for neuronal targeting. We incorporated our recently discovered rigid acrylate linking group into the initiator to retain a high degree of binding to the MOR and grafted random or block copolymers of poly(oligo(ethylene oxide) methacrylate)-block-(glycidyl methacrylate). Trifluoroethanol promoted amine ring opening of the glycidyl methacrylate was used for post-polymerization modification of the fentanyl initiated polymers to attach a near-infrared fluorescent dye (ADS790WS) or to build a targeted siRNA delivery system via modification with secondary amines. We examined the biocompatibility, cellular internalization, and siRNA binding properties of our polymer library in a green fluorescent protein expressing SY SH5Y neuroblastoma cell-line.
Neuroscience Disruptive Research Lab, Allegheny Health Network Research Institute, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.|Neuroscience Institute, Allegheny Health Network, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.
Devora
D
Cohen-Karni
Neuroscience Disruptive Research Lab, Allegheny Health Network Research Institute, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.|Neuroscience Institute, Allegheny Health Network, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.
Marina
M
Kovaliov
Neuroscience Disruptive Research Lab, Allegheny Health Network Research Institute, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.|Neuroscience Institute, Allegheny Health Network, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.
Shaohua
S
Li
Neuroscience Institute, Allegheny Health Network, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.
Stephen
S
Jaffee
Neuroscience Institute, Allegheny Health Network, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.
Nestor D
ND
Tomycz
Neuroscience Disruptive Research Lab, Allegheny Health Network Research Institute, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.|Neuroscience Institute, Allegheny Health Network, Allegheny General Hospital , Pittsburgh, Pennsylvania 15212, United States.
Saadyah
0000-0003-4775-2317
S
Averick
D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005283:Fentanyl; D005456:Fluorescent Dyes; D006801:Humans; D009447:Neuroblastoma / Q000000981:diagnostic imaging; D009474:Neurons / Q000378:metabolism; D058105:Polymerization; D011108:Polymers / Q000737:chemistry / Q000493:pharmacokinetics*; D034741:RNA, Small Interfering / Q000378:metabolism / Q000493:pharmacokinetics*; D017450:Receptors, Opioid, mu
D005456:Fluorescent Dyes; D011108:Polymers; D034741:RNA, Small Interfering; D017450:Receptors, Opioid, mu; D005283:Fentanyl