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pH-Sensitive hydrazone-linked doxorubicin nanogels via polymeric-activated ester scaffolds : synthesis, assembly, and in vitro and in vivo evaluation in tumor-bearing zebrafish

(2018) CHEMISTRY OF MATERIALS. 30(23). p.8587-8596
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Abstract
Nanoparticle conjugation is a powerful method to reduce the side effects of anticancer agents such as doxorubicin by altering the pharmacokinetic profile of the drug. Nanoparticles can prolong the circulation time and could also promote enhanced accumulation in tumors, either passively via the enhanced permeability and retention effect or actively when decorated with targeting motifs. For the particular case of doxorubicin, the hydrazone-based conjugation chemistry is popular but commonly involves laborious chemical transformation steps. Here, we report on a straightforward route for the synthesis of hydrazone-based doxorubicin polymer conjugates starting from a polymeric-activated ester scaffold onto which doxorubicin-reactive hydrazide moieties are introduced by simple treatment with hydrazine. Using block copolymers composed of a hydrophobic reactive ester block, we demonstrate a simple route to assemble core-crosslinked doxorubicin-loaded nanoparticles. The latter largely retain their bioactivity in vitro. In a zebrafish embryo "premurine" in vivo model, we demonstrate a drastic reduction in the systemic toxicity of doxorubicin upon nanoparticle conjugation and also demonstrate enhanced tumor accumulation and tumor growth reduction.
Keywords
DRUG-DELIVERY, CONTROLLED-RELEASE, TARGETED THERAPY, NANOPARTICLES, COPOLYMER, MICELLES, CHEMOTHERAPY, ENVIRONMENT, CHALLENGES, PARTICLES

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Chicago
Van Driessche, Alexandra, Agnese Kocere, Hannelien Everaert, Lutz Nuhn, Simon Van Herck, Gareth Griffiths, Federico Fenaroli, and Bruno De Geest. 2018. “pH-Sensitive Hydrazone-linked Doxorubicin Nanogels via Polymeric-activated Ester Scaffolds : Synthesis, Assembly, and in Vitro and in Vivo Evaluation in Tumor-bearing Zebrafish.” Chemistry of Materials 30 (23): 8587–8596.
APA
Van Driessche, A., Kocere, A., Everaert, H., Nuhn, L., Van Herck, S., Griffiths, G., Fenaroli, F., et al. (2018). pH-Sensitive hydrazone-linked doxorubicin nanogels via polymeric-activated ester scaffolds : synthesis, assembly, and in vitro and in vivo evaluation in tumor-bearing zebrafish. CHEMISTRY OF MATERIALS, 30(23), 8587–8596.
Vancouver
1.
Van Driessche A, Kocere A, Everaert H, Nuhn L, Van Herck S, Griffiths G, et al. pH-Sensitive hydrazone-linked doxorubicin nanogels via polymeric-activated ester scaffolds : synthesis, assembly, and in vitro and in vivo evaluation in tumor-bearing zebrafish. CHEMISTRY OF MATERIALS. 2018;30(23):8587–96.
MLA
Van Driessche, Alexandra et al. “pH-Sensitive Hydrazone-linked Doxorubicin Nanogels via Polymeric-activated Ester Scaffolds : Synthesis, Assembly, and in Vitro and in Vivo Evaluation in Tumor-bearing Zebrafish.” CHEMISTRY OF MATERIALS 30.23 (2018): 8587–8596. Print.
@article{8583640,
  abstract     = {Nanoparticle conjugation is a powerful method to reduce the side effects of anticancer agents such as doxorubicin by altering the pharmacokinetic profile of the drug. Nanoparticles can prolong the circulation time and could also promote enhanced accumulation in tumors, either passively via the enhanced permeability and retention effect or actively when decorated with targeting motifs. For the particular case of doxorubicin, the hydrazone-based conjugation chemistry is popular but commonly involves laborious chemical transformation steps. Here, we report on a straightforward route for the synthesis of hydrazone-based doxorubicin polymer conjugates starting from a polymeric-activated ester scaffold onto which doxorubicin-reactive hydrazide moieties are introduced by simple treatment with hydrazine. Using block copolymers composed of a hydrophobic reactive ester block, we demonstrate a simple route to assemble core-crosslinked doxorubicin-loaded nanoparticles. The latter largely retain their bioactivity in vitro. In a zebrafish embryo {\textacutedbl}premurine{\textacutedbl} in vivo model, we demonstrate a drastic reduction in the systemic toxicity of doxorubicin upon nanoparticle conjugation and also demonstrate enhanced tumor accumulation and tumor growth reduction.},
  author       = {Van Driessche, Alexandra and Kocere, Agnese and Everaert, Hannelien and Nuhn, Lutz and Van Herck, Simon and Griffiths, Gareth and Fenaroli, Federico and De Geest, Bruno},
  issn         = {0897-4756},
  journal      = {CHEMISTRY OF MATERIALS},
  language     = {eng},
  number       = {23},
  pages        = {8587--8596},
  title        = {pH-Sensitive hydrazone-linked doxorubicin nanogels via polymeric-activated ester scaffolds : synthesis, assembly, and in vitro and in vivo evaluation in tumor-bearing zebrafish},
  url          = {http://dx.doi.org/10.1021/acs.chemmater.8b03702},
  volume       = {30},
  year         = {2018},
}

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