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 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.

[1]  W. Meier,et al.  Stimuli-responsive polymersomes as nanocarriers for drug and gene delivery. , 2009, Macromolecular bioscience.

[2]  Guoying Zhang,et al.  Stimuli-responsive tertiary amine methacrylate-based block copolymers: Synthesis, supramolecular self-assembly and functional applications , 2014 .

[3]  P. Righetti,et al.  Protolytic equilibria of doxorubicin as determined by isoelectric focusing and ‘electrophoretic titration curves’ , 1979, FEBS letters.

[4]  D. Taton,et al.  pH and temperature responsive polymeric micelles and polymersomes by self-assembly of poly[2-(dimethylamino)ethyl methacrylate]-b-poly(glutamic acid) double hydrophilic block copolymers. , 2010, Langmuir : the ACS journal of surfaces and colloids.

[5]  Yongfeng Zhou,et al.  Enhanced gene transfection efficiency of PDMAEMA by incorporating hydrophobic hyperbranched polymer cores: effect of degree of branching , 2012 .

[6]  Jianzhong Du,et al.  Asymmetrical polymer vesicles with a "stealthy" outer corona and an endosomal-escape-accelerating inner corona for efficient intracellular anticancer drug delivery. , 2014, Biomacromolecules.

[7]  Peter Lindner,et al.  pH-induced release from P2VP-PEO block copolymer vesicles. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[8]  Chao Deng,et al.  pH and reduction dual-bioresponsive polymersomes for efficient intracellular protein delivery. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[9]  G. Battaglia,et al.  Cellular interactions with photo-cross-linked and pH-sensitive polymersomes: biocompatibility and uptake studies. , 2012, Biomacromolecules.

[10]  Timothy P. Lodge,et al.  Block Copolymers: Past Successes and Future Challenges , 2003 .

[11]  Yiyong Mai,et al.  Self-assembly of block copolymers. , 2012, Chemical Society reviews.

[12]  D. Haddleton,et al.  Synthesis and properties of polydimethylsiloxane‐containing block copolymers via living radical polymerization , 2001 .

[13]  J. Karp,et al.  Nanocarriers as an Emerging Platform for Cancer Therapy , 2022 .

[14]  S. Armes,et al.  pH-responsive vesicles based on a hydrolytically self-cross-linkable copolymer. , 2005, Journal of the American Chemical Society.

[15]  M. Bélanger,et al.  Hemocompatibility, biocompatibility, inflammatory and in vivo studies of primary reference materials low-density polyethylene and polydimethylsiloxane: a review. , 2001, Journal of biomedical materials research.

[16]  D. Haddleton,et al.  Atom Transfer Polymerization of Methyl Methacrylate Mediated by Alkylpyridylmethanimine Type Ligands, Copper(I) Bromide, and Alkyl Halides in Hydrocarbon Solution , 1999 .

[17]  S. Agarwal,et al.  PDMAEMA based gene delivery materials , 2012 .

[18]  Yebang Tan,et al.  Preparation and self-assembly behavior of polystyrene-block-poly (dimethylaminoethyl methacrylate) amphiphilic block copolymer using atom transfer radical polymerization , 2008 .

[19]  Kasper Renggli,et al.  Selective and Responsive Nanoreactors , 2011 .

[20]  D. Adams,et al.  Effect of block length, polydispersity, and salt concentration on PEO-PDEAMA block copolymer structures in dilute solution. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[21]  Cornelia G Palivan,et al.  Stimuli-Responsive Polymers and Their Applications in Nanomedicine , 2012, Biointerphases.

[22]  You Han Bae,et al.  Recent progress in tumor pH targeting nanotechnology. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[23]  I. Hamley.  Nanostructure fabrication using block copolymers , 2003 .

[24]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[25]  B. Zhang,et al.  PEGylated poly(2-(dimethylamino) ethyl methacrylate)/DNA polyplex micelles decorated with phage-displayed TGN peptide for brain-targeted gene delivery. , 2013, Biomaterials.

[26]  W. Meier,et al.  Amphiphilic PEG‐b‐PMCL‐b‐PDMAEMA Triblock Copolymers: From Synthesis to Physico‐Chemistry of Self‐Assembled Structures , 2011 .

[27]  J. Feijen,et al.  Redox and pH-responsive degradable micelles for dually activated intracellular anticancer drug release. , 2013, Journal of controlled release : official journal of the Controlled Release Society.

[28]  W. Meier,et al.  Functionalization of Block Copolymer Vesicle Surfaces , 2011 .

[29]  R. Schubert,et al.  Structure of artificial cytoskeleton containing liposomes in aqueous solution studied by static and dynamic light scattering. , 2002, Biomacromolecules.

[30]  Floris P. J. T. Rutjes,et al.  Polymeric vesicles in biomedical applications , 2011 .

[31]  D. Adams,et al.  Impact of mechanism of formation on encapsulation in block copolymer vesicles. , 2008, Journal of controlled release : official journal of the Controlled Release Society.

[32]  F. Arcamone,et al.  Self-association of doxorubicin and related compounds in aqueous solution. , 1984, Journal of pharmaceutical sciences.

[33]  P. Schwille,et al.  Photo-crosslinked and pH sensitive polymersomes for triggering the loading and release of cargo. , 2011, Chemical communications.

[34]  Andreas Walther,et al.  Janus particles: synthesis, self-assembly, physical properties, and applications. , 2013, Chemical reviews.