Multifunctional hollow nanoparticles based on graft-diblock copolymers for doxorubicin delivery

Pei Lin Lu, Yi Chun Chen, Ta Wei Ou, Hung Hao Chen, Hsieh Chih Tsai, Chih Jen Wen, Chun Liang Lo*, Shiaw Pyng Wey, Kun Ju Lin, Tzu Chen Yen, Ging Ho Hsiue

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

This article reports a flexible hollow nanoparticles, self-assembling from poly(N-vinylimidazole-co-N-vinylpyrrolidone)-g-poly(d,l-lactide) graft copolymers and methoxyl/functionalized-PEG-PLA diblock copolymers, as an anticancer drug doxorubicin (Dox) carrier for cancer targeting, imaging, and cancer therapy. This multifunctional hollow nanoparticle exhibited a specific on-off switch drug release behavior, owning to the pH-sensitive structure of imidazole, to release Dox in acidic surroundings (intracellular endosomes) and to capsulate Dox in neutral surroundings (blood circulation or extracellular matrix). Imaging by SPECT/CT shows that nanoparticle conjugated with folic acids ensures a high intratumoral accumulation due to the folate-binding protein (FBP)-binding effect. In vivo tumor growth inhibition shows that nanoparticles exhibited excellent antitumor activity and a high rate of apoptosis in cancer cells. After 80-day treatment course of nanoparticles, it did not appreciably cause heart, liver and kidney damage by inactive Dox or polymeric materials. The results indicate that the flexible carriers with an on-off switched drug release may be allowed to accurately deliver to targeted tumors for cancer therapy.

Original languageEnglish
Pages (from-to)2213-2221
Number of pages9
JournalBiomaterials
Volume32
Issue number8
DOIs
StatePublished - Mar 2011

Keywords

  • Cancer targeting
  • Cancer therapy
  • Intracellular drug delivery
  • Multifunctional hollow nanoparticles
  • SPECT/CT imaging

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