A biocompatible oxidation-triggered carrier polymer with potential in therapeutics

Kyle E. Broaders; Sirisha Grandhe; Jean M.J. Fréchet

doi:10.1021/ja110468v

A biocompatible oxidation-triggered carrier polymer with potential in therapeutics

Kyle E. Broaders, Sirisha Grandhe, Jean M.J. Fréchet

Research output: Contribution to journal › Article › peer-review

345 Scopus citations

Abstract

Dextran, a water-soluble, biocompatible polymer of glucose, was modified at its hydroxyls with arylboronic esters to make it soluble in common organic solvents, allowing for the facile preparation of oxidation-sensitive dextran (Oxi-DEX) carrier microparticles. These particles were found to release their payload with a half-life of 36 min at 1 mM H₂O₂, which can be compared with a half-life of greater than 1 week in the absence of H ₂O₂. When used in a model vaccine application, Oxi-DEX particles loaded with ovalbumin (OVA) increased the presentation to CD8 ⁺ T-cells 27-fold relative to OVA encapsulated in a classical vehicle not sensitive to oxidation. No presentation was observed from cells incubated with unencapsulated OVA Additionally, Oxi-DEX was found to be nontoxic in preliminary in vitro cytotoxicity assays. Because it is easy to prepare, sensitive to biological oxidation, and biocompatible, this material may represent an attractive new platform for selective delivery applications.

Original language	English (US)
Pages (from-to)	756-758
Number of pages	3
Journal	Journal of the American Chemical Society
Volume	133
Issue number	4
DOIs	https://doi.org/10.1021/ja110468v
State	Published - Feb 2 2011

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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10.1021/ja110468v

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abstract = "Dextran, a water-soluble, biocompatible polymer of glucose, was modified at its hydroxyls with arylboronic esters to make it soluble in common organic solvents, allowing for the facile preparation of oxidation-sensitive dextran (Oxi-DEX) carrier microparticles. These particles were found to release their payload with a half-life of 36 min at 1 mM H2O2, which can be compared with a half-life of greater than 1 week in the absence of H 2O2. When used in a model vaccine application, Oxi-DEX particles loaded with ovalbumin (OVA) increased the presentation to CD8 + T-cells 27-fold relative to OVA encapsulated in a classical vehicle not sensitive to oxidation. No presentation was observed from cells incubated with unencapsulated OVA Additionally, Oxi-DEX was found to be nontoxic in preliminary in vitro cytotoxicity assays. Because it is easy to prepare, sensitive to biological oxidation, and biocompatible, this material may represent an attractive new platform for selective delivery applications.",

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N2 - Dextran, a water-soluble, biocompatible polymer of glucose, was modified at its hydroxyls with arylboronic esters to make it soluble in common organic solvents, allowing for the facile preparation of oxidation-sensitive dextran (Oxi-DEX) carrier microparticles. These particles were found to release their payload with a half-life of 36 min at 1 mM H2O2, which can be compared with a half-life of greater than 1 week in the absence of H 2O2. When used in a model vaccine application, Oxi-DEX particles loaded with ovalbumin (OVA) increased the presentation to CD8 + T-cells 27-fold relative to OVA encapsulated in a classical vehicle not sensitive to oxidation. No presentation was observed from cells incubated with unencapsulated OVA Additionally, Oxi-DEX was found to be nontoxic in preliminary in vitro cytotoxicity assays. Because it is easy to prepare, sensitive to biological oxidation, and biocompatible, this material may represent an attractive new platform for selective delivery applications.

AB - Dextran, a water-soluble, biocompatible polymer of glucose, was modified at its hydroxyls with arylboronic esters to make it soluble in common organic solvents, allowing for the facile preparation of oxidation-sensitive dextran (Oxi-DEX) carrier microparticles. These particles were found to release their payload with a half-life of 36 min at 1 mM H2O2, which can be compared with a half-life of greater than 1 week in the absence of H 2O2. When used in a model vaccine application, Oxi-DEX particles loaded with ovalbumin (OVA) increased the presentation to CD8 + T-cells 27-fold relative to OVA encapsulated in a classical vehicle not sensitive to oxidation. No presentation was observed from cells incubated with unencapsulated OVA Additionally, Oxi-DEX was found to be nontoxic in preliminary in vitro cytotoxicity assays. Because it is easy to prepare, sensitive to biological oxidation, and biocompatible, this material may represent an attractive new platform for selective delivery applications.

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A biocompatible oxidation-triggered carrier polymer with potential in therapeutics

Abstract

ASJC Scopus subject areas

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