title: Development of Surface-Variable Polymeric Nanoparticles for Drug Delivery to Tumors.
abstract: To develop nanoparticle drug carriers that interact with cells specifically in the mildly acidic tumor microenvironment, we produced polymeric nanoparticles modified with amidated TAT peptide via a simple surface modification method. Two types of core poly(lactic-co-glycolic acid) nanoparticles (NL and NP) were prepared with a phospholipid shell as an optional feature and covered with polydopamine that enabled the conjugation of TAT peptide on the surface. Subsequent treatment with acid anhydrides such as cis-aconitic anhydride (CA) and succinic anhydride (SA) converted amines of lysine residues in TAT peptide to β-carboxylic amides, introducing carboxylic groups that undergo pH-dependent protonation and deprotonation. The nanoparticles modified with amidated TAT peptide (NLpT-CA and NPpT-CA) avoided interactions with LS174T colon cancer cells and J774A.1 macrophages at pH 7.4 but restored the ability to interact with LS174T cells at pH 6.5, delivering paclitaxel efficiently to the cells following a brief contact time. In LS174T tumor-bearing nude mice, NPpT-CA showed less accumulation in the lung than NPpT, reflecting the shielding effect of amidation, but tumor accumulation of NPpT and NPpT-CA was equally minimal. Comparison of particle stability and protein corona formation in media containing sera from different species suggests that NPpT-CA has been activated and opsonized in mouse blood to a greater extent than those in bovine serum-containing medium, thus losing the benefits of pH-sensitivity expected from in vitro experiments.
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University , 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.|Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University , 103 Wenhua Road, Shenyang, Liaoning 110016, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Han
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University , 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.|Department of Pharmaceutics, School of Pharmacy, Fudan University , 826 Zhangheng Road, Shanghai 201203, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Pang
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University , 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University , 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.
authors.forename: Hyesun
authors.initials: H
authors.lastname: Hyun
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University , 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.|Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company , Indianapolis, Indiana 46285, United States.
authors.forename: Jinho
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Industrial and Physical Pharmacy, Purdue University , 575 Stadium Mall Drive, West Lafayette, Indiana 47907, United States.|Weldon School of Biomedical Engineering, Purdue University , 206 South Martin Jischke Drive, West Lafayette, Indiana 47907, United States.
authors.forename: Yoon
authors.identifier: 0000-0001-9505-7701
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D008819:Mice, Nude; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010455:Peptides; D011108:Polymers; D054322:tat Gene Products, Human Immunodeficiency Virus; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
keywords: PLGA nanoparticles; TAT peptide; acid anhydrides; drug delivery; pH sensitive