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  • Title: Degradable poly(beta-amino ester) nanoparticles for cancer cytoplasmic drug delivery.
    Author: Shen Y, Tang H, Zhan Y, Van Kirk EA, Murdoch WJ.
    Journal: Nanomedicine; 2009 Jun; 5(2):192-201. PubMed ID: 19223244.
    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.
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