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Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin.

Newland B, Leupelt D, Zheng Y, Thomas LS, Werner C, Steinhart M, Wang W - Sci Rep (2015)

Bottom Line: Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency.Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template.Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Centre for Biomaterials Dresden, Hohe Straße. 6, Dresden 01069, Germany.

ABSTRACT
Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers, and various therapeutics.

No MeSH data available.


Related in: MedlinePlus

A simple “one-pot” route to a photocrosslinkable pre-polymer.The homopolymerization of EGDMA via in situ Deactivation Enhanced ATRP (DE-ATRP) allows the formation of a growing chain and intramolecular cyclizations. In the early reaction phases a knot structured polymer is produced, however, at later stages these knots combine via traditional intermolecular branches.
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f1: A simple “one-pot” route to a photocrosslinkable pre-polymer.The homopolymerization of EGDMA via in situ Deactivation Enhanced ATRP (DE-ATRP) allows the formation of a growing chain and intramolecular cyclizations. In the early reaction phases a knot structured polymer is produced, however, at later stages these knots combine via traditional intermolecular branches.

Mentions: Much research into the delivery of therapeutics via nanotubes has focused on the use of graphitic carbon nanotubes with subsequent surface functionalization to covalently bind a cargo17. Carbon structures containing a nanoscopic open pore (termed carbon nanopipes) have been synthesized within an AAO template181920 but this process requires carbon vapor deposition at high temperatures limiting the capacity for in situ functionalization of the tubes. Herein we develop a homopolymer designed to be photocrosslinkable within the pores of an AAO template and thus allow the formation of hollow nanotubes at room temperature. Figure 1 depicts the “deactivation enhanced” modification of atom transfer radical polymerization (ATRP) required for the synthesis of a homopolymer from the bifunctional vinyl monomer ethylene glycol dimethacrylate (EGDMA)21. Traditionally the inclusion of only a few percent of a multi-vinyl monomer in an ATRP co-polymerization would result in the formation of an insoluble crosslinked gel22 unsuitable for further study. However, recently we have shown that deactivation enhanced ATRP (DE-ATRP) can control the synthesis (reduce the kinetic chain length and therefore growth boundary) to such an extent as to allow homopolymerization of EGDMA into single soluble chains2123. In this study, we synthesize these chains, which contain internal cyclizations (intramolecular crosslinks) and free (unreacted) vinyl groups depicted in Fig. 1 as overlapping chains (blue circles) and free double bonds sticking out of the chain. However, at later reaction stages, as free monomers become more exhausted and cyclized knot chain concentrations are high, the cyclized chains combine to form multiple knots joined by intermolecular crosslinks24, shown as a green circle in Fig. 1.


Magnetically Controllable Polymer Nanotubes from a Cyclized Crosslinker for Site-Specific Delivery of Doxorubicin.

Newland B, Leupelt D, Zheng Y, Thomas LS, Werner C, Steinhart M, Wang W - Sci Rep (2015)

A simple “one-pot” route to a photocrosslinkable pre-polymer.The homopolymerization of EGDMA via in situ Deactivation Enhanced ATRP (DE-ATRP) allows the formation of a growing chain and intramolecular cyclizations. In the early reaction phases a knot structured polymer is produced, however, at later stages these knots combine via traditional intermolecular branches.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664922&req=5

f1: A simple “one-pot” route to a photocrosslinkable pre-polymer.The homopolymerization of EGDMA via in situ Deactivation Enhanced ATRP (DE-ATRP) allows the formation of a growing chain and intramolecular cyclizations. In the early reaction phases a knot structured polymer is produced, however, at later stages these knots combine via traditional intermolecular branches.
Mentions: Much research into the delivery of therapeutics via nanotubes has focused on the use of graphitic carbon nanotubes with subsequent surface functionalization to covalently bind a cargo17. Carbon structures containing a nanoscopic open pore (termed carbon nanopipes) have been synthesized within an AAO template181920 but this process requires carbon vapor deposition at high temperatures limiting the capacity for in situ functionalization of the tubes. Herein we develop a homopolymer designed to be photocrosslinkable within the pores of an AAO template and thus allow the formation of hollow nanotubes at room temperature. Figure 1 depicts the “deactivation enhanced” modification of atom transfer radical polymerization (ATRP) required for the synthesis of a homopolymer from the bifunctional vinyl monomer ethylene glycol dimethacrylate (EGDMA)21. Traditionally the inclusion of only a few percent of a multi-vinyl monomer in an ATRP co-polymerization would result in the formation of an insoluble crosslinked gel22 unsuitable for further study. However, recently we have shown that deactivation enhanced ATRP (DE-ATRP) can control the synthesis (reduce the kinetic chain length and therefore growth boundary) to such an extent as to allow homopolymerization of EGDMA into single soluble chains2123. In this study, we synthesize these chains, which contain internal cyclizations (intramolecular crosslinks) and free (unreacted) vinyl groups depicted in Fig. 1 as overlapping chains (blue circles) and free double bonds sticking out of the chain. However, at later reaction stages, as free monomers become more exhausted and cyclized knot chain concentrations are high, the cyclized chains combine to form multiple knots joined by intermolecular crosslinks24, shown as a green circle in Fig. 1.

Bottom Line: Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency.Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template.Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes.

View Article: PubMed Central - PubMed

Affiliation: Leibniz Institute of Polymer Research Dresden, Max Bergmann Centre for Biomaterials Dresden, Hohe Straße. 6, Dresden 01069, Germany.

ABSTRACT
Externally controlled site specific drug delivery could potentially provide a means of reducing drug related side effects whilst maintaining, or perhaps increasing therapeutic efficiency. The aim of this work was to develop a nanoscale drug carrier, which could be loaded with an anti-cancer drug and be directed by an external magnetic field. Using a single, commercially available monomer and a simple one-pot reaction process, a polymer was synthesized and crosslinked within the pores of an anodized aluminum oxide template. These polymer nanotubes (PNT) could be functionalized with iron oxide nanoparticles for magnetic manipulation, without affecting the large internal pore, or inherent low toxicity. Using an external magnetic field the nanotubes could be regionally concentrated, leaving areas devoid of nanotubes. Lastly, doxorubicin could be loaded to the PNTs, causing increased toxicity towards neuroblastoma cells, rendering a platform technology now ready for adaptation with different nanoparticles, degradable pre-polymers, and various therapeutics.

No MeSH data available.


Related in: MedlinePlus