Nanomedicine: Nanotechnology, Biology and Medicine
Volume 5, Issue 2 , Pages 192-201, June 2009

Degradable Poly(β-amino ester) nanoparticles for cancer cytoplasmic drug delivery

  • Youqing Shen, PhD

      Affiliations

    • Center for Bionanoengineering and Nanomedicine and Department of Chemical and Biochemical Engineering, College of Materials Science and Chemical Engineering, Zhejiang University, Hangzhou, China
    • Soft Materials Laboratory, Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, Wyoming, USA
    • Corresponding Author InformationCorresponding author. Soft Materials Laboratory, Department of Chemical and Petroleum Engineering, University of Wyoming, P.O. Box 3295, Laramie, Wyoming 82071-3295, USA.
    • ,
  • Huadong Tang, PhD

      Affiliations

    • Soft Materials Laboratory, Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, Wyoming, USA
    • ,
  • Yihong Zhan, BS

      Affiliations

    • Soft Materials Laboratory, Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, Wyoming, USA
    • ,
  • Edward A. Van Kirk, MS

      Affiliations

    • Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA
    • ,
  • William J. Murdoch, PhD

      Affiliations

    • Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA

Received 7 December 2007; accepted 20 September 2008. published online 29 September 2008.

Abstract 

Fast cytoplasmic drug delivery can overcome cancer cells' drug resistance and thus have an enhanced therapeutic efficacy. Such a drug delivery regime requires drug carriers capable of entering cancer cells, localizing and rapidly releasing the drug into endosomes/lysosomes, and subsequently disrupting their membranes to release the drug into the cytosol. We herein report a low-toxic and degradable poly(β-amino ester)-graft-polyethylene glycol (BAE-PEG) co-polymer forming pH-responsive nanoparticles capable of cytoplasmic drug delivery. BAE-PEG was synthesized by condensation polymerization of diacrylate and piperazine in the presence of a PEG-diacrylate macromonomer. BAE-PEG with 2% or 5% PEG side chains formed micelles (nanoparticles) with diameters of about 100 nm. The BAE-PEG nanoparticles were shown to rapidly enter cancer cells, localize in their endosomes/lysosomes, and subsequently disrupt them to release the drugs into the cytosol. Camptothecin loaded in the nanoparticles had a higher cytotoxicity to SKOV-3 ovarian cancer cells than free camptothecin.

Key words: Cytoplasmic drug delivery, pH-responsive nanoparticles, Graft polymers, Lysosomal escape

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 Financial support of this work originated from the China National Science Fund for Distinguished Young Scholars and the American Cancer Society (RSG-06-118-01-CDD). No support came from any commercial associations.

PII: S1549-9634(08)00149-4

doi:10.1016/j.nano.2008.09.003

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 5, Issue 2 , Pages 192-201, June 2009

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