pH-Responsive PDMS‑b‑PDMAEMA Micelles for Intracellular Anticancer Drug Delivery

A series of poly(dimethysiloxane)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMS-b-PDMAEMA) block copolymers were synthesized with atom transfer radical polymerization (ATRP). In aqueous solution the polymers self-assembled into micelles with diameters between 80 and 300 nm, with the ability to e...

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Bibliographic Details
Published in:Biomacromolecules 2014-09, Vol.15 (9), p.3235-3245
Main Authors: Car, Anja, Baumann, Patric, Duskey, Jason T, Chami, Mohamed, Bruns, Nico, Meier, Wolfgang
Format: Article
Language:English
Subjects:
Antibiotics, Antineoplastic - chemistry
Antibiotics, Antineoplastic - pharmacokinetics
Antibiotics, Antineoplastic - pharmacology
Dimethylpolysiloxanes - chemistry
Dimethylpolysiloxanes - pharmacokinetics
Dimethylpolysiloxanes - pharmacology
Doxorubicin - chemistry
Doxorubicin - pharmacokinetics
Doxorubicin - pharmacology
Drug Carriers - chemistry
Drug Carriers - pharmacokinetics
Drug Carriers - pharmacology
Endocytosis - drug effects
HeLa Cells
Humans
Hydrogen-Ion Concentration
Methacrylates - chemistry
Methacrylates - pharmacokinetics
Methacrylates - pharmacology
Micelles
Nanoparticles - chemistry
Nylons - chemistry
Nylons - pharmacokinetics
Nylons - pharmacology
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Summary:A series of poly(dimethysiloxane)-b-poly(2-(dimethylamino)ethyl methacrylate) (PDMS-b-PDMAEMA) block copolymers were synthesized with atom transfer radical polymerization (ATRP). In aqueous solution the polymers self-assembled into micelles with diameters between 80 and 300 nm, with the ability to encapsulate DOX. The polymer with the shortest PDMAEMA block (5 units) displayed excellent cell viability, while micelles containing longer PDMAEMA block lengths (13 and 22 units) led to increased cytotoxicity. The carriers released DOX in response to a decrease in pH from 7.4 to 5.5. Confocal laser scanning microscopy (CLSM) revealed that nanoparticles were taken up by endocytosis into acidic cell compartments. Furthermore, DOX-loaded nanocarriers exhibited intracellular pH-response as changes in cell morphology and drug release were observed within 24 h.
ISSN:1525-7797
1526-4602
DOI:10.1021/bm500919z