Degradable poly(beta-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(beta-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.

• Authors: Youqing Shen, Huadong Tang, Yihong Zhan, Edward A Van Kirk, William J Murdoch
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 5 Issue 2 Pg. 192-201 (Jun 2009) ISSN: 1549-9642 [Electronic] United States
• PMID: 19223244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Piperazines
• Polymers
• poly(beta-amino ester)
• Polyethylene Glycols
• Camptothecin

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Camptothecin (administration & dosage, chemistry)
• Cell Line, Tumor
• Cytosol (drug effects)
• Drug Carriers (chemistry, metabolism)
• Endosomes (metabolism)
• Humans
• Hydrogen-Ion Concentration
• Microscopy, Confocal
• Nanoparticles (chemistry, toxicity)
• Piperazines (chemistry, metabolism, toxicity)
• Polyethylene Glycols (chemistry, metabolism, toxicity)
• Polymers (chemistry, metabolism, toxicity)
• Sheep