Bi‐Enzymatic Embolization Beads for Two‐Armed Enzyme‐Prodrug Therapy

Morten Tobias Jarlstad Olesen; Anna Winther; Betina Fejerskov; Frederik Dagnæs-Hansen; Ulf Simonsen; Alexander N. Zelikin

doi:10.1002/adtp.201800023

Bi‐Enzymatic Embolization Beads for Two‐Armed Enzyme‐Prodrug Therapy

Morten Tobias Jarlstad Olesen, Anna Winther, Betina Fejerskov, Frederik Dagnæs-Hansen, Ulf Simonsen, Alexander N. Zelikin

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

11 Citations (Scopus)

Abstract

Embolic beads, a successful tool for localized, site-specific drug delivery, are engineered herein to contain the toolbox of enzyme-prodrug therapy (EPT). EPT offers facile means to synthesize diverse drugs at their nominated concentrations; individually, in sequence, or in a combination. The authors investigate alginate beads as embolic bodies and screen alginate type and bead production parameters as factors to control activity of the immobilized enzymes. Engineered embolic bodies are armed with bi-enzymatic EPT such that two enzymes perform biosynthesis of drugs with an independent control over each enzyme. Enzymatic synthesis of nitric oxide (NO) performed by embolic bodies is accomplished herein for the first time and is fine-tuned such that flux of NO afforded by the beads matches that of healthy human endothelium. Ensuing vasodilation is illustrated ex vivo using rat mesenteric arteries. Independently, the production of SN-38 is used to control the antiproliferative effects elicited by the beads. Bi-enzymatic EPT engineered into embolic bodies thus affords opportunities for combination therapy and personalized treatment (adjusted combinations and concentrations of drugs) that go well beyond the state-of-the-art of current embolic bodies and hold much promise for biomedical applications, specifically the treatment of hepatocellular carcinoma.

Original language	Danish
Article number	1800023
Journal	Advanced Therapeutics
Volume	1
Issue	4
Number of pages	9
ISSN	2366-3987
DOIs	https://doi.org/10.1002/adtp.201800023
Publication status	Published - 1 Aug 2018

Keywords

SN-38
combination therapy
embolization beads
enzyme-prodrug therapy
nitric oxide

Access to Document

10.1002/adtp.201800023

Cite this

@article{808f46f5276f446aa7b06a52d180f530,

title = "Bi‐Enzymatic Embolization Beads for Two‐Armed Enzyme‐Prodrug Therapy",

abstract = "Embolic beads, a successful tool for localized, site-specific drug delivery, are engineered herein to contain the toolbox of enzyme-prodrug therapy (EPT). EPT offers facile means to synthesize diverse drugs at their nominated concentrations; individually, in sequence, or in a combination. The authors investigate alginate beads as embolic bodies and screen alginate type and bead production parameters as factors to control activity of the immobilized enzymes. Engineered embolic bodies are armed with bi-enzymatic EPT such that two enzymes perform biosynthesis of drugs with an independent control over each enzyme. Enzymatic synthesis of nitric oxide (NO) performed by embolic bodies is accomplished herein for the first time and is fine-tuned such that flux of NO afforded by the beads matches that of healthy human endothelium. Ensuing vasodilation is illustrated ex vivo using rat mesenteric arteries. Independently, the production of SN-38 is used to control the antiproliferative effects elicited by the beads. Bi-enzymatic EPT engineered into embolic bodies thus affords opportunities for combination therapy and personalized treatment (adjusted combinations and concentrations of drugs) that go well beyond the state-of-the-art of current embolic bodies and hold much promise for biomedical applications, specifically the treatment of hepatocellular carcinoma.",

keywords = "SN-38, combination therapy, embolization beads, enzyme-prodrug therapy, nitric oxide",

author = "Olesen, {Morten Tobias Jarlstad} and Anna Winther and Betina Fejerskov and Frederik Dagn{\ae}s-Hansen and Ulf Simonsen and Zelikin, {Alexander N.}",

year = "2018",

month = aug,

day = "1",

doi = "10.1002/adtp.201800023",

language = "Dansk",

volume = "1",

journal = "Advanced Therapeutics",

issn = "2366-3987",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "4",

}

TY - JOUR

T1 - Bi‐Enzymatic Embolization Beads for Two‐Armed Enzyme‐Prodrug Therapy

AU - Olesen, Morten Tobias Jarlstad

AU - Winther, Anna

AU - Fejerskov, Betina

AU - Dagnæs-Hansen, Frederik

AU - Simonsen, Ulf

AU - Zelikin, Alexander N.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Embolic beads, a successful tool for localized, site-specific drug delivery, are engineered herein to contain the toolbox of enzyme-prodrug therapy (EPT). EPT offers facile means to synthesize diverse drugs at their nominated concentrations; individually, in sequence, or in a combination. The authors investigate alginate beads as embolic bodies and screen alginate type and bead production parameters as factors to control activity of the immobilized enzymes. Engineered embolic bodies are armed with bi-enzymatic EPT such that two enzymes perform biosynthesis of drugs with an independent control over each enzyme. Enzymatic synthesis of nitric oxide (NO) performed by embolic bodies is accomplished herein for the first time and is fine-tuned such that flux of NO afforded by the beads matches that of healthy human endothelium. Ensuing vasodilation is illustrated ex vivo using rat mesenteric arteries. Independently, the production of SN-38 is used to control the antiproliferative effects elicited by the beads. Bi-enzymatic EPT engineered into embolic bodies thus affords opportunities for combination therapy and personalized treatment (adjusted combinations and concentrations of drugs) that go well beyond the state-of-the-art of current embolic bodies and hold much promise for biomedical applications, specifically the treatment of hepatocellular carcinoma.

AB - Embolic beads, a successful tool for localized, site-specific drug delivery, are engineered herein to contain the toolbox of enzyme-prodrug therapy (EPT). EPT offers facile means to synthesize diverse drugs at their nominated concentrations; individually, in sequence, or in a combination. The authors investigate alginate beads as embolic bodies and screen alginate type and bead production parameters as factors to control activity of the immobilized enzymes. Engineered embolic bodies are armed with bi-enzymatic EPT such that two enzymes perform biosynthesis of drugs with an independent control over each enzyme. Enzymatic synthesis of nitric oxide (NO) performed by embolic bodies is accomplished herein for the first time and is fine-tuned such that flux of NO afforded by the beads matches that of healthy human endothelium. Ensuing vasodilation is illustrated ex vivo using rat mesenteric arteries. Independently, the production of SN-38 is used to control the antiproliferative effects elicited by the beads. Bi-enzymatic EPT engineered into embolic bodies thus affords opportunities for combination therapy and personalized treatment (adjusted combinations and concentrations of drugs) that go well beyond the state-of-the-art of current embolic bodies and hold much promise for biomedical applications, specifically the treatment of hepatocellular carcinoma.

KW - SN-38

KW - combination therapy

KW - embolization beads

KW - enzyme-prodrug therapy

KW - nitric oxide

UR - http://www.scopus.com/inward/record.url?scp=85085117453&partnerID=8YFLogxK

U2 - 10.1002/adtp.201800023

DO - 10.1002/adtp.201800023

M3 - Tidsskriftartikel

SN - 2366-3987

VL - 1

JO - Advanced Therapeutics

JF - Advanced Therapeutics

IS - 4

M1 - 1800023

ER -

Bi‐Enzymatic Embolization Beads for Two‐Armed Enzyme‐Prodrug Therapy

Abstract

Keywords

Access to Document

Other files and links

Cite this