title: Polydopamine-based surface modification for the development of peritumorally activatable nanoparticles.
abstract: OBJECTIVE
  To create poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), where a drug-encapsulating NP core is covered with polyethylene glycol (PEG) in a normal condition but exposes a cell-interactive TAT-modified surface in an environment rich in matrix metalloproteinases (MMPs).
  
  
  METHODS
  PLGA NPs were modified with TAT peptide (PLGA-pDA-TAT NPs) or dual-modified with TAT peptide and a conjugate of PEG and MMP-substrate peptide (peritumorally activatable NPs, PANPs) via dopamine polymerization. Cellular uptake of fluorescently labeled NPs was observed with or without a pre-treatment of MMP-2 by confocal microscopy and flow cytometry. NPs loaded with paclitaxel (PTX) were tested against SKOV-3 ovarian cancer cells to evaluate the contribution of surface modification to cellular delivery of PTX.
  
  
  RESULTS
  While the size and morphology did not significantly change due to the modification, NPs modified with dopamine polymerization were recognized by their dark color. TAT-containing NPs (PLGA-pDA-TAT NPs and PANPs) showed changes in surface charge, indicative of effective conjugation of TAT peptide on the surface. PLGA-pDA-TAT NPs and MMP-2-pre-treated PANPs showed relatively good cellular uptake compared to PLGA NPs, MMP-2-non-treated PANPs, and NPs with non-cleavable PEG. After 3 h treatment with cells, PTX loaded in cell-interactive NPs showed greater toxicity than non-interactive ones as the former could enter cells during the incubation period. However, due to the initial burst drug release, the difference was not as clear as microscopic observation.
  
  
  CONCLUSIONS
  PEGylated polymeric NPs that could expose cell-interactive surface in response to MMP-2 were successfully created by dual modification of PLGA NPs using dopamine polymerization.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, Indiana 47907, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Gullotti
authors.forename: Joonyoung
authors.initials: J
authors.lastname: Park
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D000595:Amino Acid Sequence; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D015696:Gene Products, tat / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D015696:Gene Products, tat; D007211:Indoles; D010455:Peptides; D011108:Polymers; C568283:polydopamine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D020778:Matrix Metalloproteinase 2; D017239:Paclitaxel