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Development of a Vinyl Ether-Functionalized Polyphosphoester as a Template for Multiple Postpolymerization Conjugation Chemistries and Study of Core Degradable Polymeric Nanoparticles.

Lim YH, Heo GS, Rezenom YH, Pollack S, Raymond JE, Elsabahy M, Wooley KL - Macromolecules (2014)

Bottom Line: This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries-thiol-ene "click" reaction, acetalization, or thio-acetalization reaction-to afford modified polymers that accommodated either stable thio-ether or hydrolytically labile acetal or thio-acetal linkages.Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy.The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry.

View Article: PubMed Central - PubMed

Affiliation: Departments of Chemistry, Chemical Engineering, and Materials Science and Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012, United States.

ABSTRACT

A novel polyphosphoester (PPE) with vinyl ether side chain functionality was developed as a versatile template for postpolymerization modifications, and its degradability and biocompatibility were evaluated. An organo-catalyzed ring-opening polymerization of ethylene glycol vinyl ether-pendant cyclic phosphotriester monomer allowed for construction of poly(ethylene glycol vinyl ether phosphotriester) (PEVEP). This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries-thiol-ene "click" reaction, acetalization, or thio-acetalization reaction-to afford modified polymers that accommodated either stable thio-ether or hydrolytically labile acetal or thio-acetal linkages. Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy. The stability of the micelles and the hydrolytic degradability of the backbone and side chains of the PEVEP block segment were assessed by DLS and nuclear magnetic resonance spectroscopy ((1)H and (31)P), respectively, in aqueous buffer solutions at pH values of 5.0 and 7.4 and at temperatures of 25 and 37 °C. The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry. The parent micelles and their degradation products were found to be non-cytotoxic at concentrations up to 3 mg/mL, when evaluated with RAW 264.7 mouse macrophages and OVCAR-3 human ovarian adenocarcinoma cells.

No MeSH data available.


Related in: MedlinePlus

Cytotoxicityof the parent micelles of mPEG44-b-PEVEP337 (black line) and theirdegradation products 8 (red line) at a concentrationrange of 3–3000 μg/mL for 24 h in RAW 264.7 mouse macrophages(a) and OVCAR-3 human ovarian adenocarcinoma cells (b).
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fig8: Cytotoxicityof the parent micelles of mPEG44-b-PEVEP337 (black line) and theirdegradation products 8 (red line) at a concentrationrange of 3–3000 μg/mL for 24 h in RAW 264.7 mouse macrophages(a) and OVCAR-3 human ovarian adenocarcinoma cells (b).

Mentions: The cytotoxicities of the parent micelles, 7, and their degradation products, 8, were evaluatedtoward two cell lines, RAW 264.7 mouse macrophages and OVCAR-3 humanovarian adenocarcinoma cells, at a concentration range from 3 to 3000μg/mL for 24 h (Figure 8). Both 7 and 8 maintained high cell viability over therange of the tested concentrations in both cell lines. We have previouslyobserved low cytotoxicity and immunotoxicity of PPE-based micelleswith different surface charges, their shell cross-linked analogues,and their degradation products even though we were not able to identifythe degradation products at that time.50 These PPE-based nanoparticles are expected to have broad implicationsin clinical nanomedicine as alternative vehicles to those involvedin several of the currently available medications, with precise controlover their molecular structures and overall architectures.


Development of a Vinyl Ether-Functionalized Polyphosphoester as a Template for Multiple Postpolymerization Conjugation Chemistries and Study of Core Degradable Polymeric Nanoparticles.

Lim YH, Heo GS, Rezenom YH, Pollack S, Raymond JE, Elsabahy M, Wooley KL - Macromolecules (2014)

Cytotoxicityof the parent micelles of mPEG44-b-PEVEP337 (black line) and theirdegradation products 8 (red line) at a concentrationrange of 3–3000 μg/mL for 24 h in RAW 264.7 mouse macrophages(a) and OVCAR-3 human ovarian adenocarcinoma cells (b).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296319&req=5

fig8: Cytotoxicityof the parent micelles of mPEG44-b-PEVEP337 (black line) and theirdegradation products 8 (red line) at a concentrationrange of 3–3000 μg/mL for 24 h in RAW 264.7 mouse macrophages(a) and OVCAR-3 human ovarian adenocarcinoma cells (b).
Mentions: The cytotoxicities of the parent micelles, 7, and their degradation products, 8, were evaluatedtoward two cell lines, RAW 264.7 mouse macrophages and OVCAR-3 humanovarian adenocarcinoma cells, at a concentration range from 3 to 3000μg/mL for 24 h (Figure 8). Both 7 and 8 maintained high cell viability over therange of the tested concentrations in both cell lines. We have previouslyobserved low cytotoxicity and immunotoxicity of PPE-based micelleswith different surface charges, their shell cross-linked analogues,and their degradation products even though we were not able to identifythe degradation products at that time.50 These PPE-based nanoparticles are expected to have broad implicationsin clinical nanomedicine as alternative vehicles to those involvedin several of the currently available medications, with precise controlover their molecular structures and overall architectures.

Bottom Line: This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries-thiol-ene "click" reaction, acetalization, or thio-acetalization reaction-to afford modified polymers that accommodated either stable thio-ether or hydrolytically labile acetal or thio-acetal linkages.Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy.The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry.

View Article: PubMed Central - PubMed

Affiliation: Departments of Chemistry, Chemical Engineering, and Materials Science and Engineering, Laboratory for Synthetic-Biologic Interactions, Texas A&M University, P.O. Box 30012, 3255 TAMU, College Station, Texas 77842-3012, United States.

ABSTRACT

A novel polyphosphoester (PPE) with vinyl ether side chain functionality was developed as a versatile template for postpolymerization modifications, and its degradability and biocompatibility were evaluated. An organo-catalyzed ring-opening polymerization of ethylene glycol vinyl ether-pendant cyclic phosphotriester monomer allowed for construction of poly(ethylene glycol vinyl ether phosphotriester) (PEVEP). This vinyl ether-functionalized PPE scaffold was coupled with hydroxyl- or thiol-containing model small molecules via three different types of conjugation chemistries-thiol-ene "click" reaction, acetalization, or thio-acetalization reaction-to afford modified polymers that accommodated either stable thio-ether or hydrolytically labile acetal or thio-acetal linkages. Amphiphilic diblock copolymers of poly(ethylene glycol) and PEVEP formed well-defined micelles with a narrow and monomodal size distribution in water, as confirmed by dynamic light scattering (DLS), transmission electron microscopy, and atomic force microscopy. The stability of the micelles and the hydrolytic degradability of the backbone and side chains of the PEVEP block segment were assessed by DLS and nuclear magnetic resonance spectroscopy ((1)H and (31)P), respectively, in aqueous buffer solutions at pH values of 5.0 and 7.4 and at temperatures of 25 and 37 °C. The hydrolytic degradation products of the PEVEP segments of the block copolymers were then identified by electrospray ionization, gas chromatography, and matrix-assisted laser desorption/ionization mass spectrometry. The parent micelles and their degradation products were found to be non-cytotoxic at concentrations up to 3 mg/mL, when evaluated with RAW 264.7 mouse macrophages and OVCAR-3 human ovarian adenocarcinoma cells.

No MeSH data available.


Related in: MedlinePlus