Delivery of Inorganic Polyphosphate into Cells Using Amphipathic Oligocarbonate Transporters

Overview

Journal ACS Cent Sci

Specialty Chemistry

Date 2018 Nov 10

PMID 30410977

Citations 12

Authors

Gabriella M Fernandes-Cunha

Colin J McKinlay

Jessica R Vargas

Henning J Jessen

Robert M Waymouth

Paul A Wender

Affiliations

Soon will be listed here.

Abstract

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. This general approach to polyP delivery enables the study of intracellular polyP signaling in a variety of applications.

Citing Articles

Monodisperse Chemical Oligophosphorylation of Peptides via Protected Oligophosphorimidazolide Reagents.

Qian K, Hanf B, Cummins C, Fiedler D Angew Chem Int Ed Engl. 2024; 64(11):e202419147.

PMID: 39625829 PMC: 11891630. DOI: 10.1002/anie.202419147.

Encapsulation of Inositol Hexakisphosphate with Chitosan via Gelation to Facilitate Cellular Delivery and Programmed Cell Death in Human Breast Cancer Cells.

Kadhim I, Oluremi A, Chhetri B, Ghosh A, Ali N Bioengineering (Basel). 2024; 11(9).

PMID: 39329673 PMC: 11429465. DOI: 10.3390/bioengineering11090931.

An Update on Polyphosphate In Vivo Activities.

Schoeppe R, Waldmann M, Jessen H, Renne T Biomolecules. 2024; 14(8).

PMID: 39199325 PMC: 11352482. DOI: 10.3390/biom14080937.

Biocompatible aggregation-induced emission active polyphosphate-manganese nanosheets with glutamine synthetase-like activity in excitotoxic nerve cells.

Wang J, Zhao X, Tao Y, Wang X, Yan L, Yu K Nat Commun. 2024; 15(1):3534.

PMID: 38670989 PMC: 11053040. DOI: 10.1038/s41467-024-47947-5.

The Physiological Inorganic Polymers Biosilica and Polyphosphate as Key Drivers for Biomedical Materials in Regenerative Nanomedicine.

Muller W, Neufurth M, Wang S, Schroder H, Wang X Int J Nanomedicine. 2024; 19:1303-1337.

PMID: 38348175 PMC: 10860874. DOI: 10.2147/IJN.S446405.

References

Ruiz F, Lea C, Oldfield E, Docampo R . Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J Biol Chem. 2004; 279(43):44250-7. DOI: 10.1074/jbc.M406261200. View

Brown M, Kornberg A . Inorganic polyphosphate in the origin and survival of species. Proc Natl Acad Sci U S A. 2004; 101(46):16085-7. PMC: 528972. DOI: 10.1073/pnas.0406909101. View

Han K, Hong B, Yoon Y, Yoon C, Kim Y, Kwon Y . Polyphosphate blocks tumour metastasis via anti-angiogenic activity. Biochem J. 2007; 406(1):49-55. PMC: 1948993. DOI: 10.1042/BJ20061542. View

McKinlay C, Vargas J, Blake T, Hardy J, Kanada M, Contag C . Charge-altering releasable transporters (CARTs) for the delivery and release of mRNA in living animals. Proc Natl Acad Sci U S A. 2017; 114(4):E448-E456. PMC: 5278438. DOI: 10.1073/pnas.1614193114. View

Dick E, Matsa E, Bispham J, Reza M, Guglieri M, Staniforth A . Two new protocols to enhance the production and isolation of human induced pluripotent stem cell lines. Stem Cell Res. 2010; 6(2):158-67. DOI: 10.1016/j.scr.2010.10.002. View

Prosperi E . Intracellular turnover of fluorescein diacetate. Influence of membrane ionic gradients on fluorescein efflux. Histochem J. 1990; 22(4):227-33. DOI: 10.1007/BF02386009. View

McKinlay C, Waymouth R, Wender P . Cell-Penetrating, Guanidinium-Rich Oligophosphoesters: Effective and Versatile Molecular Transporters for Drug and Probe Delivery. J Am Chem Soc. 2016; 138(10):3510-7. PMC: 5351964. DOI: 10.1021/jacs.5b13452. View

Donovan A, Kalkowski J, Smith S, Morrissey J, Liu Y . Size-controlled synthesis of granular polyphosphate nanoparticles at physiologic salt concentrations for blood clotting. Biomacromolecules. 2014; 15(11):3976-84. PMC: 8808366. DOI: 10.1021/bm501046t. View

Crouchet E, Saad R, Affolter-Zbaraszczuk C, Ogier J, Baumert T, Schuster C . Composite vector formulation for multiple siRNA delivery as a host targeting antiviral in a cell culture model of hepatitis C virus (HCV) infection. J Mater Chem B. 2020; 5(4):858-865. PMC: 7613424. DOI: 10.1039/c6tb01718e. View

10.

Azevedo C, Livermore T, Saiardi A . Protein polyphosphorylation of lysine residues by inorganic polyphosphate. Mol Cell. 2015; 58(1):71-82. DOI: 10.1016/j.molcel.2015.02.010. View

11.

Hernandez-Ruiz L, Gonzalez-Garcia I, Castro C, Brieva J, Ruiz F . Inorganic polyphosphate and specific induction of apoptosis in human plasma cells. Haematologica. 2006; 91(9):1180-6. View

12.

Matsa E, Rajamohan D, Dick E, Young L, Mellor I, Staniforth A . Drug evaluation in cardiomyocytes derived from human induced pluripotent stem cells carrying a long QT syndrome type 2 mutation. Eur Heart J. 2011; 32(8):952-62. PMC: 3076668. DOI: 10.1093/eurheartj/ehr073. View

13.

Benner N, Near K, Bachmann M, Contag C, Waymouth R, Wender P . Functional DNA Delivery Enabled by Lipid-Modified Charge-Altering Releasable Transporters (CARTs). Biomacromolecules. 2018; 19(7):2812-2824. PMC: 6542359. DOI: 10.1021/acs.biomac.8b00401. View

14.

Prosperi E, Croce A, Bottiroli G, Supino R . Flow cytometric analysis of membrane permeability properties influencing intracellular accumulation and efflux of fluorescein. Cytometry. 1986; 7(1):70-5. DOI: 10.1002/cyto.990070110. View

15.

Sun T, Zhang Y, Pang B, Hyun D, Yang M, Xia Y . Engineered nanoparticles for drug delivery in cancer therapy. Angew Chem Int Ed Engl. 2014; 53(46):12320-64. DOI: 10.1002/anie.201403036. View

16.

Azevedo C, Singh J, Steck N, Hofer A, Ruiz F, Singh T . Screening a Protein Array with Synthetic Biotinylated Inorganic Polyphosphate To Define the Human PolyP-ome. ACS Chem Biol. 2018; 13(8):1958-1963. DOI: 10.1021/acschembio.8b00357. View

17.

Blanco E, Shen H, Ferrari M . Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat Biotechnol. 2015; 33(9):941-51. PMC: 4978509. DOI: 10.1038/nbt.3330. View

18.

Hassanian S, Dinarvand P, Smith S, Rezaie A . Inorganic polyphosphate elicits pro-inflammatory responses through activation of the mammalian target of rapamycin complexes 1 and 2 in vascular endothelial cells. J Thromb Haemost. 2015; 13(5):860-71. PMC: 4424178. DOI: 10.1111/jth.12899. View

19.

Contag C, Spilman S, Contag P, Oshiro M, Eames B, Dennery P . Visualizing gene expression in living mammals using a bioluminescent reporter. Photochem Photobiol. 1997; 66(4):523-31. DOI: 10.1111/j.1751-1097.1997.tb03184.x. View

20.

Lander N, Cordeiro C, Huang G, Docampo R . Polyphosphate and acidocalcisomes. Biochem Soc Trans. 2016; 44(1):1-6. PMC: 4879816. DOI: 10.1042/BST20150193. View