title: Enhanced cell penetration of acid-degradable particles functionalized with cell-penetrating peptides.
abstract: Biopharmaceuticals, such as proteins and DNA, have demonstrated their potential to prevent and cure diseases. The success of such therapeutic agents hinges upon their ability to cross complex barriers in the body and reach their target intact. In order to reap the full benefits of these therapeutic agents, a delivery vehicle capable of delivering cargo to all cell types, both phagocytic and non-phagocytic, is needed. This article presents the synthesis and evaluation of a microparticle delivery vehicle capable of cell penetration and sub-cellular triggered release of an encapsulated payload. pH-sensitive polyacrylamide particles functionalized with a polyarginine cell-penetrating peptide (CPP) were synthesized. The incorporation of a CPP into the microparticles led to efficient uptake by non-phagocytic cells in culture. In addition, the CPP-modified particles showed no cytotoxic effects at concentrations used in this study. The results suggest that these particles may provide a vehicle for the successful delivery of therapeutic agents to various cell types.
authors.affiliation: College of Chemistry, University of California, Berkeley, California 94720-1460, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Cohen
authors.forename: Adah
authors.initials: A
authors.lastname: Almutairi
authors.forename: Joel A
authors.initials: JA
authors.lastname: Cohen
authors.forename: Matt
authors.initials: M
authors.lastname: Bernstein
authors.forename: Steven L
authors.initials: SL
authors.lastname: Brody
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Schuster
authors.forename: Jean M J
authors.initials: JM
authors.lastname: Fréchet
mesh_terms: D000143:Acids / Q000737:chemistry*; D000180:Acrylic Resins / Q000737:chemistry; D001692:Biological Transport; D003432:Cross-Linking Reagents / Q000737:chemistry; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D000099166:Polyacrylamides
chemical_list: D000143:Acids; D000180:Acrylic Resins; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D010455:Peptides; D011108:Polymers; D000099166:Polyacrylamides