title: Self-assembled micelles of amphiphilic poly(L-phenylalanine)-b-poly(L-serine) polypeptides for tumor-targeted delivery.
abstract: The aim of this work was to design, synthesize, and characterize self-assembled micelles based on polypeptides as a potential antitumor drug carrier. Amphiphilic poly(L-phenylalanine)-b-poly(L-serine) (PFS) polypeptides were obtained through the polymerization of N-carboxyanhydride. As a novel hydrophilic segment, poly(L-serine) was utilized to enhance tumor targeting due to a large demand of tumors for serine. PFS could self-assemble into micelles with an average diameter of 110-240 nm and a slightly negative charge. PFS polypeptides adopted random coil in pH 7.4 phosphate-buffered saline and could partly transform to α-helix induced by trifluoroethanol. PFS micelles with a low critical micelle concentration of 4.0 μg mL(-1) were stable in pH 5-9 buffers and serum albumin solution. PFS micelles had a loading capacity of 3.8% for coumarin-6 and exhibited a sustained drug release. Coumarin-6 loaded rhodamine B isothiocyanate-labeled PFS micelles were incubated with Huh-7 tumor cells to study the correlation between drugs and carriers during endocytosis. The uptake of drugs was consistent with the micelles, illustrating that the intracellular transport of drugs highly depended on the micelles. PFS micelles diffused in whole cytoplasm while coumarin-6 assumed localized distribution, suggesting that the micelles could release the loaded drugs in particular areas. The internalization mechanism of PFS micelles was involved with clathrin-mediated endocytosis and macropinocytosis. Excess serine inhibited the uptake of PFS micelles, which demonstrated that serine receptors played a positive role in the internalization of PFS. The more interesting thing was that the uptake inhibition impacted on normal cells but not on tumor cells at the physiological concentration of serine. The difference in the uptake of PFS micelles was fourfold as high between the tumor cells and the normal cells, which indicated that PFS micelles had good tumor targeting in vitro. In conclusion, PFS micelles reported in this work were a promising drug delivery system for tumor targeting therapy.
authors.affiliation: Department of Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China ; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China ; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China ; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.affiliation: Department of Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Keli
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China ; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China ; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China ; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Basic Medical Sciences, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Yuanjian
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China ; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, Xuzhou, People's Republic of China.
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Yin
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008823:Micelles; D010455:Peptides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D010455:Peptides; C027794:polyserine; C012001:polyphenylalanine
keywords: amphiphilic polypeptides; micelles; poly(l-phenylalanine); poly(l-serine); tumor therapy