title: A biodegradable pH-sensitive micelle system for targeting acidic solid tumors.
abstract: A new pH-sensitive micelle delivery system based on TAT cell penetrating peptide and biodegradable sulfonamide grafted disulfide polymer is presented. The system consists of two components: (1) A polymeric micelle made of Poly(L-lactic acid)-b-poly(ethylene glycol) (PLLA-b-PEG) conjugated to TAT (TAT-micelle), (2) A pH-sensitive diblock copolymer (poly(L-cystine bisamide-g-sulfadiazine))-b-PEG (PCBS-b-PEG). The anionic PCBS complexed with cationic TAT of TAT-micelles forms the final carrier. PCBS showed rapid degradation in the presence of cysteine. The TAT-micelles showed increase in particle size between pH 8.0 and 7.0 upon mixing with PCBS-b-PEG indicating complexation. As the pH was further decreased (pH 6.8 to 6.0) two populations were observed, one of normal TAT-micelles and the other of aggregated PCBS-b-PEG. Flow cytometry showed significantly higher uptake of TAT-micelles at pH 6.6 indicating deshielding compared to pH 7.4. The anticancer drug doxorubicin (DOX) was encapsulated into the TAT-micelles, and the in vitro cytotoxicity at different pHs was evaluated. The system was able to distinguish pHs 7.2 and 7.0 in terms of cytotoxicity.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, Utah 84108, USA.
authors.forename: Vijay A
authors.initials: VA
authors.lastname: Sethuraman
authors.forename: Myung Cheon
authors.initials: MC
authors.lastname: Lee
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001672:Biocompatible Materials; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers; D004339:Drug Compounding; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000737:chemistry; D008823:Micelles; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013411:Sulfadiazine / Q000737:chemistry; D015534:Trans-Activators / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D007773:Lactates; D008823:Micelles; D010446:Peptide Fragments; D010455:Peptides; D011108:Polymers; D015534:Trans-Activators; C088513:poly(lactic acid-ethylene glycol); D013411:Sulfadiazine; D011092:Polyethylene Glycols; C057713:polycysteine; D004317:Doxorubicin