title: Developing a Dissociative Nanocontainer for Peptide Drug Delivery.
abstract: The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB) models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP) reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid) is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers.
authors.affiliation: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. mkelly3@gc.cuny.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kelly
authors.affiliation: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. prachiacbr.du@gmail.com.
authors.forename: Prachi
authors.initials: P
authors.lastname: Anand
authors.affiliation: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. auvaydov21@gmail.com.
authors.forename: Alexander
authors.initials: A
authors.lastname: Uvaydov
authors.affiliation: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. sc82@hunter.cuny.edu.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Chakravartula
authors.affiliation: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. chhime11@gmail.com.
authors.forename: Chhime
authors.initials: C
authors.lastname: Sherpa
authors.affiliation: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. pirele92@gmail.com.
authors.forename: Elena
authors.initials: E
authors.lastname: Pires
authors.affiliation: Stem Cell and Regenerative Biology Department, Harvard University, 7 Divinity Ave, Cambridge, MA 02138, USA. alisonloneil@gmail.com.
authors.forename: Alison
authors.initials: A
authors.lastname: O'Neil
authors.affiliation: Department of Chemistry, Indiana University, 800 E. Kirkwood Ave., Bloomington, IN 47405, USA. trevdoug@indiana.edu.
authors.forename: Trevor
authors.initials: T
authors.lastname: Douglas
authors.affiliation: Hunter College and The Graduate Center, City University of New York, Belfer Research Building, 413 E. 69th Street, New York, NY 10021, USA. mholford@hunter.cuny.edu.|The American Museum of Natural History, Central Park West & 79th Street, New York, NY 10024, USA. mholford@hunter.cuny.edu.
authors.forename: Mandë
authors.initials: M
authors.lastname: Holford
mesh_terms: D017100:Bacteriophage P22 / Q000737:chemistry*; D036022:Capsid Proteins / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D053769:Nanocapsules / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*
chemical_list: D036022:Capsid Proteins; D053769:Nanocapsules; D010455:Peptides
keywords: Grubbs catalyst; P22 bacteriophage; ROMP; controlled disassembly; drug delivery; nanocontainers; peptide therapeutics; triggered release; venom peptides; viral capsid