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1.
Proc Natl Acad Sci U S A ; 114(45): E9437-E9444, 2017 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-29078379

RESUMEN

The interaction of fields with condensed matter during phase transitions produces a rich variety of physical phenomena. Self-assembly of liquid crystalline block copolymers (LC BCPs) in the presence of a magnetic field, for example, can result in highly oriented microstructures due to the LC BCP's anisotropic magnetic susceptibility. We show that such oriented mesophases can be produced using low-intensity fields (<0.5 T) that are accessible using permanent magnets, in contrast to the high fields (>4 T) and superconducting magnets required to date. Low-intensity field alignment is enabled by the addition of labile mesogens that coassemble with the system's nematic and smectic A mesophases. The alignment saturation field strength and alignment kinetics have pronounced dependences on the free mesogen concentration. Highly aligned states with orientation distribution coefficients close to unity were obtained at fields as small as 0.2 T. This remarkable field response originates in an enhancement of alignment kinetics due to a reduction in viscosity, and increased magnetostatic energy due to increases in grain size, in the presence of labile mesogens. These developments provide routes for controlling structural order in BCPs, including the possibility of producing nontrivial textures and patterns of alignment by locally screening fields using magnetic nanoparticles.

2.
Pharmacol Res ; 107: 93-101, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-26976795

RESUMEN

We previously reported the development of an amphiphilic brush-like block copolymer composed of polynorbornene-cholesterol/polyethylene glycol (P(NBCh9-b-NBPEG)) that self-assembles in aqueous media to form long circulating nanostructures capable of encapsulating doxorubicin (DOX-NPs). Biodistribution studies showed that this formulation preferentially accumulates in tumor tissue with markedly reduced accumulation in the heart and other major organs. The aim of the current study was to evaluate the in vivo efficacy and toxicity of DOX containing self-assembled polymer nanoparticles in a mouse xenograft tumor model and compare its effects with the hydrochloride non-encapsulated form (free DOX). DOX-NPs significantly reduced the growth of tumors without inducing any apparent toxicity. Conversely, mice treated with free DOX exhibited significant weight loss, early toxic cardiomyopathy, acute toxic hepatopathy, reduced hematopoiesis and fatal toxicity. The improved safety profile of the polymeric DOX-NPs can be explained by the low circulating concentration of non-nanoparticle-associated drug as well as the reduced accumulation of DOX in non-target organs. These findings support the use of P(NBCh9-b-NBPEG) nanoparticles as delivery platforms for hydrophobic anticancer drugs intended to reduce the toxicity of conventional treatments.


Asunto(s)
Antineoplásicos , Colesterol/química , Doxorrubicina , Nanopartículas , Células A549 , Alanina Transaminasa/sangre , Animales , Antineoplásicos/efectos adversos , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapéutico , Doxorrubicina/efectos adversos , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/uso terapéutico , Hígado/efectos de los fármacos , Hígado/patología , Ratones SCID , Miocardio/patología , Nanopartículas/efectos adversos , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias/sangre , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Bazo/efectos de los fármacos , Bazo/patología , Troponina I/sangre , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
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