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

• Published in: Nanomedicine Vol. 5; no. 2; pp. 192 - 201
• Main Authors: Shen, Youqing, PhD, Tang, Huadong, PhD, Zhan, Yihong, BS, Van Kirk, Edward A., MS, Murdoch, William J., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2009
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Camptothecin - administration & dosage; Camptothecin - chemistry; Cell Line, Tumor; Cytoplasmic drug delivery; Cytosol - drug effects; Drug Carriers - chemistry; Drug Carriers - metabolism; Endosomes - metabolism; Graft polymers; Humans; Hydrogen-Ion Concentration; Internal Medicine; Lysosomal escape; Microscopy, Confocal; Nanoparticles - chemistry; Nanoparticles - toxicity; pH-responsive nanoparticles; Piperazines - chemistry; Piperazines - metabolism; Piperazines - toxicity; Polyethylene Glycols - chemistry; Polyethylene Glycols - metabolism; Polyethylene Glycols - toxicity; Polymers - chemistry; Polymers - metabolism; Polymers - toxicity; Sheep; Cytoplasmic drug delivery; pH-responsive nanoparticles; Graft polymers; Lysosomal escape
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2008.09.003

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.