Degradable Poly(β-amino ester) nanoparticles for cancer cytoplasmic drug delivery
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.
aCenter for Bionanoengineering and Nanomedicine and Department of Chemical and Biochemical Engineering, College of Materials Science and Chemical Engineering, Zhejiang University, Hangzhou, China
bSoft Materials Laboratory, Department of Chemical and Petroleum Engineering, University of Wyoming, Laramie, Wyoming, USA
cDepartment of Animal Science, University of Wyoming, Laramie, Wyoming, USA
Corresponding author. Soft Materials Laboratory, Department of Chemical and Petroleum Engineering, University of Wyoming, P.O. Box 3295, Laramie, Wyoming 82071-3295, USA.
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.
ABSTRACT