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Your search keyword '"Shi, Haili"' showing total 2 results
Start Over Author "Shi, Haili" Topic acrylic acid
2 results on '"Shi, Haili"'

1. Polymeric Micelles Employing Platinum(II) Linker for the Delivery of the Kinase Inhibitor Dactolisib

Author

Shi, Haili, Lou, Bo, van Steenbergen, Mies J., Sijbrandi, Niels J., Hennink, Wim E., Kok, Robbert J., Afd Pharmaceutics, Pharmaceutics, Afd Pharmaceutics, and Pharmaceutics

Subjects
Chemistry(all), Ethylenediamine, 02 engineering and technology, Micelle, chemistry.chemical_compound, 020401 chemical engineering, Materials Science(all), PEG ratio, kinase inhibitors, General Materials Science, 0204 chemical engineering, Acrylic acid, polymeric micelles, Chemistry, General Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Drug delivery, drug delivery, coordination chemistry, polymer–metal complexes, Nanocarriers, 0210 nano-technology, Linker, Ethylene glycol, Nuclear chemistry
Abstract

Polymeric micelles are attractive nanocarriers for hydrophobic drug molecules such as the kinase inhibitor dactolisib. Two different poly(ethylene glycol)–poly(acrylic acid) (PEG-b-PAA) block-copolymers are synthesized, PEG(5400)-b-PAA(2000) and PEG(10000)-b-PAA(3700), respectively. Polymeric micelles are formed by self-assembly once dactolisib is conjugated via the ethylenediamine platinum(II) linker (Lx) to the PAA block of the block copolymers. Dactolisib micelles with dactolisib loading content of 17% w/w show good colloidal stability and display sustained release of Lx-dactolisib over 96 h in PBS at 37 °C, while media containing reagents that compete for platinum coordination (e.g., glutathione (GSH) or dithiothreitol (DTT)) effectuate release of the parent inhibitor dactolisib at similar release rates. Dactolisib/lissamine-loaded micelles are internalized by human breast adenocarcinoma cells (MCF-7) in a dose and time-dependent manner as demonstrated by confocal microscopy. Dactolisib-loaded micelles inhibit the PI3K/mTOR signaling pathway at low concentrations (400 × 10−9 m) and exhibit potent cytotoxicity against MCF-7 cells with IC50 values of 462 ± 46 and 755 ± 75 × 10−9 m for micelles with either short or longer PEG-b-PAA block lengths. In conclusion, dactolisib loaded PEG-b-PAA micelles are successfully prepared and hold potential for nanomedicine-based tumor delivery of dactolisib.

Published
2019

2. Folate decorated polymeric micelles for targeted delivery of the kinase inhibitor dactolisib to cancer cells.

Author

Shi, Haili, van Steenbergen, Mies J., Lou, Bo, Liu, Yanna, Hennink, Wim E., and Kok, Robbert J.

Subjects
*MICELLES, *FOLIC acid, *KINASE inhibitors, *CANCER cells, *ACRYLIC acid, *ETHYLENE glycol
Abstract

One of the main challenges in clinical translation of polymeric micelles is retention of the drug in the nanocarrier system upon its systemic administration. Core crosslinking and coupling of the drug to the micellar backbone are common strategies to overcome these issues. In the present study, polymeric micelles were prepared for tumor cell targeting of the kinase inhibitor dactolisib which inhibits both the mammalian Target of Rapamycin (mTOR) kinase and phosphatidylinositol-3-kinase (PI3K). We employed platinum(II)-based linker chemistry to couple dactolisib to the core of poly(ethylene glycol)- b -poly(acrylic acid) (PEG- b -PAA) polymeric micelles. The formed dactolisib-PEG-PAA unimers are amphiphilic and self-assemble in an aqueous milieu into core–shell polymeric micelles. Folate was conjugated onto the surface of the micelles to yield folate-decorated polymeric micelles which can target folate receptor over-expressing tumor cells. Fluorescently labeled polymeric micelles were prepared using a lissamine-platinum complex linked in a similar manner as dactolisib. Dactolisib polymeric micelles showed good colloidal stability in water and released the coupled drug in buffers containing chloride or glutathione. Folate decorated micelles were avidly internalized by folate-receptor-positive KB cells and displayed targeted cellular cytotoxicity at 50–75 nM IC 50. In conclusion, we have prepared a novel type of folate-receptor targeted polymeric micelles in which platinum(II) linker chemistry modulates drug retention and sustained release of the coupled inhibitor dactolisib. [ABSTRACT FROM AUTHOR]

Published
2020
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