Multidrug resistance (MDR), which is related to cancer chemotherapy, tumor stem cells, and tumor metastasis, is a huge obstacle for the effective cancer therapy. One of the underlying mechanisms of MDR is the increased efflux of anticancer drugs by overexpressed P-glycoprotein (P-gp) of multidrug resistant cells. In this work, the antibody of P-gp (anti-P-gp) functionalized water-soluble single-walled carbon nanotubes (Ap-SWNTs) loaded with doxorubicin (Dox), Dox/Ap-SWNTs, were synthesized for challenging the MDR of K562 human leukemia cells. The resulting Ap-SWNTs could not only specifically recognize the multidrug resistant human leukemia cells (K562R), but also demonstrate the effective loading and controllable release performance for Dox toward the target K562R cells by exposing to near-infrared radiation (NIR). The recognition capability of Ap-SWNTs toward the K562R cells was confirmed by flow cytometry (FCM) and confocal laser scanning microscopy (CLSM). The binding affinity of Ap-SWNTs toward drug-resistant K562R cells was ca. 23-fold higher than that toward drug-sensitive K562S cells. Additionally, CLSM indicated that Ap-SWNTs could specifically localize on the cell membrane of K562R cells and the fluorescence of Dox in K562R cells could be significantly enhanced after the employment of Ap-SWNTs as carrier. Moreover, the composite of Dox and Ap-SWNTs (Dox/Ap-SWNTs) expressed 2.4-fold higher cytotoxicity and showed the significant cell proliferation suppression toward K562R leukemia cells (p < 0.05) as compared with free Dox which is popularly employed in clinic trials. These results suggest that the Ap-SWNTs are the promising drug delivery vehicle for overcoming the MDR induced by the overexpression of P-gp on cell membrane. Ap-SWNTs loaded with drug molecules could be used to suppress the proliferation of multidrug resistant cells, destroy the tumor stem cells, and inhibit the metastasis of tumor.
A "one-pot" process for the preparation of organic-silica hybrid capillary monolithic columns by concurrently using organic monomers and alkoxysilanes was described. In this process, the hydrolyzed alkoxysilanes of tetramethoxysilane (TMOS) and vinyltrimethoxysilane (VTMS) as precursors for the synthesis of a silica-based monolith using the sol-gel method and the organic monomer (allyldimethyldodecylammonium bromide (ADDAB) or acrylamide (AA)) with vinyl groups for free radical polymerization along with the initiator of azobisisobutyronitrile (AIBN) were concurrently introduced into a pretreated capillary; after that, the polycondensation of alkoxysilanes and the copolymerization of organic monomers and as-precondensed siloxanes were subsequently carried out within the confines of a capillary at the proper reaction conditions. Two types of organic-silica hybrid capillary monolithic columns with hydrophobic and hydrophilic properties have been fabricated, respectively, by this "one-pot" process using two different organic monomers of ADDAB and AA. The morphologies of the synthesized organic-silica hybrid monolithic columns were characterized by scanning electron microscopy (SEM). The performances of these organic-silica monolithic columns were investigated by capillary electrochromatography (CEC). The retention behaviors of the neutral and polar compounds on the resulting hydrophobic and hydrophilic organic-silica hybrid monolithic columns confirmed the successful incorporation of organic monomers in the silica monolithic matrix. In addition, the ADDA-silica hybrid capillary monolithic column was also applied in the analysis of tryptic digests of bovine serum albumin (BSA) and mouse liver extract by microliquid chromatography-tandem mass spectrometry (microLC-MS/MS) for demonstrating its potential in proteome analysis.
Perphenylcarbamoylated β-cyclodextrin-silica (Ph-β-CD-silica) hybrid monolithic columns for enantioseparation in capillary liquid chromatography (cLC) have been prepared by a "one-pot" approach via the polycondensation of alkoxysilanes and in situ copolymerization of mono (6(A)-N-allylamino-6(A)-deoxy)-Ph-β-CD and vinyl group on the precondensed siloxanes. The morphologies of the Ph-β-CD-silica hybrid monolithic columns were characterized by optical microscopy and scanning electron microscopy (SEM), showing the uniform monolithic matrixes tightly bonded onto the capillary wall. The content of Ph-β-CD incorporated in monolithic matrix by the "one-pot" approach was ca. 2.9 times higher than that by postmodification method. The permeability of the Ph-β-CD-silica chiral hybrid monolithic column was 3.63 × 10(-14) m(2), and the minimum plate height was 12 μm corresponding to 83,300 theoretical plates/meter. Enantioseparations of 13 racemates were achieved by the Ph-β-CD-silica hybrid monolithic column. In this work, since the prepolymerization system mainly consisted of organic solvent (methanol (MeOH), N,N-dimethylformamide (DMF)), the limitation and difficulty of the use of water insoluble organic monomers in the previously reported "one-pot" method was circumvented. Therefore, various β-CD derivatives as well as other hydrophobic monomers could thus be used to prepare organic-silica hybrid monolithic columns with the "one-pot" process.
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