title: 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.affiliation: Center for Bionanoengineering and Nanomedicine and Department of Chemical and Biochemical Engineering, College of Materials Science and Chemical Engineering, Zhejiang University, Hangzhou, China. shenyq@zju.edu.cn
authors.forename: Youqing
authors.initials: Y
authors.lastname: Shen
authors.forename: Huadong
authors.initials: H
authors.lastname: Tang
authors.forename: Yihong
authors.initials: Y
authors.lastname: Zhan
authors.forename: Edward A
authors.initials: EA
authors.lastname: Van Kirk
authors.forename: William J
authors.initials: WJ
authors.lastname: Murdoch
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D003600:Cytosol / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D011108:Polymers / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D012756:Sheep
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010879:Piperazines; D011108:Polymers; C507253:poly(beta-amino ester); D011092:Polyethylene Glycols; D002166:Camptothecin