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.

Micelles as potential drug delivery systems for colorectal cancer treatment

“…Chemically conjugated drugs are released by bulk degradation or surface erosion of the micelles, while the physically entrapped drugs are mainly released by diffusion[ 38 ]. Intact drug-loaded micelles are internalized via cell- dependent pinocytosis, which includes macropinocytosis, clathrin-mediated endocytosis, caveolae-mediated endocytosis and clathrin- and caveolae-independent endocytosis[ 39 - 42 ] . Internalized micelles have been shown to localize in acidic organelles, namely endosomes or lysosomes[ 40 , 43 ].…”

Combined Shikonin-Loaded MPEG-PCL Micelles Inhibits Effective Transition of Endothelial-to-Mesenchymal Cells

“…The in vitro cellular uptake of MPEG-PCL micelles loaded with the fluorescent probe coumarin 6 (Tokyo Chemical Industry, Japan) was assessed according to a previously described method with some modifications. 32 , 33 Briefly, a sample (100 μL) of the micelles was mixed with 400 μL distilled water and 500 μL acetonitrile and vortexed for 30s before the amount of coumarin 6 loaded in the MPEG-PCL micelles was determined by HPLC under the conditions listed in Table 1 .…”

Polypeptide-Based Systems: From Synthesis to Application in Drug Delivery

“…A general outline of such a synthetic approach is shown in Figure 7. In most cases, the initially obtained homopolypeptide macroinitiator is isolated from the reaction mixture and purified, and after that, the synthesis of the block copol- In most cases, the initially obtained homopolypeptide macroinitiator is isolated from the reaction mixture and purified, and after that, the synthesis of the block copolymer is performed [18,[80][81][82][83]. However, there are publications in which the interaction of the obtained macroinitiator with the following NCA is carried out without its preliminary isolation.…”