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Title: Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters

Journal Article · · ACS Central Science

Inorganic polyphosphate (polyP) is an often-overlooked biopolymer of phosphate residues present in living cells. PolyP is associated with many essential biological roles. Despite interest in polyP’s function, most studies have been limited to extracellular or isolated protein experiments, as polyanionic polyP does not traverse the nonpolar membrane of cells. To address this problem, we developed a robust, readily employed method for polyP delivery using guanidinium-rich oligocarbonate transporters that electrostatically complex polyPs of multiple lengths, forming discrete nanoparticles that are resistant to phosphatase degradation and that readily enter multiple cell types. Fluorescently labeled polyPs have been monitored over time for subcellular localization and release from the transporter, with control over release rates achieved by modulating the transporter identity and the charge ratio of the electrostatic complexes. Furthermore, this general approach to polyP delivery enables the study of intracellular polyP signaling in a variety of applications.

Research Organization:
Leland Stanford Junior Univ., Palo Alto, CA (United States); Stanford Univ., CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
Grant/Contract Number:
SC0018168
OSTI ID:
1474016
Alternate ID(s):
OSTI ID: 1483936; OSTI ID: 1508740
Journal Information:
ACS Central Science, Vol. 4, Issue 10; ISSN 2374-7943
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 11 works
Citation information provided by
Web of Science

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Synthesis and Evaluation of Chromogenic and Fluorogenic Substrates for High-Throughput Detection of Enzymes That Hydrolyze Inorganic Polyphosphate journal July 2014
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Targeted polyphosphatase expression alters mitochondrial metabolism and inhibits calcium-dependent cell death journal November 2007
Designed guanidinium-rich amphipathic oligocarbonate molecular transporters complex, deliver and release siRNA in cells journal July 2012
Inorganic polyphosphate stimulates mammalian TOR, a kinase involved in the proliferation of mammary cancer cells journal September 2003
Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals journal January 2017
Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters journal June 2018
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Inorganic polyphosphate is a potent activator of the mitochondrial permeability transition pore in cardiac myocytes journal April 2012
Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation journal March 2011
Inorganic polyphosphate elicits pro-inflammatory responses through activation of the mammalian target of rapamycin complexes 1 and 2 in vascular endothelial cells journal April 2015
Inorganic Polyphosphate: A Molecule of Many Functions journal June 1999
Induction of Calcification in MC3T3-E1 Cells by Inorganic Polyphosphate journal August 2004
Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation journal June 2012
Amorphous, Smart, and Bioinspired Polyphosphate Nano/Microparticles: A Biomaterial for Regeneration and Repair of Osteo-Articular Impairments In-Situ journal January 2018

Cited By (6)

A Phosphoramidite Analogue of Cyclotriphosphate Enables Iterative Polyphosphorylations journal February 2019
A Phosphoramidite Analogue of Cyclotriphosphate Enables Iterative Polyphosphorylations journal March 2019
Cyclotriphosphate: A Brief History, Recent Developments, and Perspectives in Synthesis journal December 2019
Supramolecular caging for cytosolic delivery of anionic probes journal January 2019
Cyclotriphosphate: A Brief History, Recent Developments, and Perspectives in Synthesis journal December 2019
A Broad Response to Intracellular Long-Chain Polyphosphate in Human Cells journal October 2020

Figures / Tables (6)