title: Poly(L-aspartic acid) nanogels for lysosome-selective antitumor drug delivery.
abstract: Advanced materials that have controllable pH-responsive properties when submerged in the lysosome have a great potential in intracellular drug delivery. We developed novel poly(L-amino acid) nanogels that were prepared by a facile cross-linking of poly[L-aspartic acid-g-(3-diethylaminopropyl)]-b-poly(ethylene glycol)-maleimide [poly(L-Asp-g-DEAP)-b-PEG-Mal] and poly(L-aspartic acid-g-ethyl thiol)-b-PEG [poly(L-Asp-SH)-b-PEG] in an oil/water emulsion condition. Interestingly, these nanogels (~125 nm in diameter) modulated volume expansion (~375 nm in diameter) in a lysosomal pH (~pH 5.0) due to an extensive proton absorption of DEAP at a low pH, which mediated lysosome swelling and the subsequent lysosome destabilization. In the in vitro tumor cell cytotoxicity test, they encouraged tumor cell death, probably owing to the leakage of lysosomal enzymes. Furthermore, encapsulating antitumor drug (e.g., doxorubicin, DOX) into these nanogels enhanced tumor cell cytotoxicity. We conclude that this nanogel system will have great potential for tumor therapy.
authors.affiliation: Division of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Nam Muk
authors.initials: NM
authors.lastname: Oh
authors.forename: Kyung Taek
authors.initials: KT
authors.lastname: Oh
authors.forename: Yu Seok
authors.initials: YS
authors.lastname: Youn
authors.forename: Deok-Keun
authors.initials: DK
authors.lastname: Lee
authors.forename: Kyung-Hoi
authors.initials: KH
authors.lastname: Cha
authors.forename: Don Haeng
authors.initials: DH
authors.lastname: Lee
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Lee
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004318:Doxycycline / Q000008:administration & dosage / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009113:Muramidase / Q000737:chemistry*; D049329:Nanostructures; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D010051:Ovarian Neoplasms / Q000188:drug therapy; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D004337:Drug Carriers; D005782:Gels; D010455:Peptides; C017645:polyaspartate; D009113:Muramidase; D004318:Doxycycline