Volume 5, Issue 2 , Pages 192-201, June 2009
Degradable Poly(β-amino ester) nanoparticles for cancer cytoplasmic drug delivery
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
© 2009 Elsevier Inc. All rights reserved.
Volume 5, Issue 2 , Pages 192-201, June 2009
