RESUMO
A novel amphiphilic ABA-type triblock copolymer poly(ethylene glycol)-b-poly(ethanedithiol-alt-nitrobenzyl)-b-poly(ethylene glycol) (PEG-b-PEDNB-b-PEG) is successfully prepared by sequential thiol-acrylate Michael addition polymerization in one pot. PEG-b-PEDNB-b-PEG is designed to have light-cleavable o-nitrobenzyl linkages and acid-labile ß-thiopropionate linkages positioned repeatedly in the main chain of the hydrophobic block. The light and pH dual degradation of PEG-b-PEDNB-b-PEG is traced by gel permeation chromatography (GPC). Such triblock copolymer can self-assemble into micelles, which can be used to encapsulate anticancer drug doxorubicin (DOX). Because of the different degradation chemistry of o-nitrobenzyl linkages and ß-thiopropionate linkages, DOX can be released from the micelles by two different manners, i.e., light-induced rapid burst release and pH-induced slow sustained release. Confocal laser scanning microscopy (CLSM) results indicated that DOX-loaded micelles exhibited faster drug release in A549 cells after UV irradiation. Furthermore, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results show that the DOX-loaded micelles under UV light degradation exhibit better anticancer activity against A549 cells than that of the nonirradiated ones.
Assuntos
Antimetabólitos Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , Micelas , Polímeros/química , Raios Ultravioleta , Antimetabólitos Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Química Click , Preparações de Ação Retardada , Doxorrubicina/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Polímeros/síntese química , Polímeros/isolamento & purificaçãoRESUMO
The title mol-ecule, C(5)H(4)O(2)S(3), consists of a planar [mean deviation = 0.020â (1)â Å] 1,3-dithiole-2-thione unit with an ethyl-enedi-oxy group in the 4,5-positions. The dioxine ring is in a twist-chair conformation.
RESUMO
In the title compound, C(22)H(21)BrO, other than the Br atom, the non-H atoms are approximately co-planar [maxium deviation = 0.178â (2)â Å] and the alk-oxy chain shows an all-anti conformation. A weak inter-molecular C-Hâ¯Br hydrogen bond contributes to the stabilization of the crystal structure.
RESUMO
In this letter, light-responsive protein-encapsulated polyion complex (PIC) micelles were prepared by self-assembly of cationic block copolymer poly(N,N-dimethyl-N-(2-(methacryloyloxy)ethyl)-N-((2-nitrobenzyl)oxy)-2-oxoethanaminium bromide)-block-poly(carboxybetaine methacrylate) (PDMNBMA-b-PCBMA) and negatively charged bovine serum albumin (BSA). The PIC micelles were well characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). From the zeta potential measurement, the increase of the zeta potential of PIC micelles from â¼10 to â¼20 mV was observed when the solution pH decreased from 7.4 to 6.5, which could enhance the intracellular protein delivery efficiency. Moreover, the positively charged PDMNBMA blocks can be transformed to zwitterionic carboxybetaine units under UV irradiation, which could result in the disassembly of the PIC micelles. The release of BSA can therefore be drastically accelerated in the presence of UV irradiation. Meanwhile, the circular dichroism (CD) spectroscopy confirmed that the secondary structure of BSA was unaffected during the UV irradiation process.