کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6539 499 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
pH-responsive complexes using prefunctionalized polymers for synchronous delivery of doxorubicin and siRNA to cancer cells
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی بیو مهندسی (مهندسی زیستی)
پیش نمایش صفحه اول مقاله
pH-responsive complexes using prefunctionalized polymers for synchronous delivery of doxorubicin and siRNA to cancer cells
چکیده انگلیسی

A nanocarrier delivery system that can simultaneously deliver a chemotherapeutic drug and siRNA to the tumor is emerging as a promising treatment strategy for cancer treatment. In this study, a multifunctional PHD/PPF/siRNA complexes was developed by one-step assembly of prefunctionalized polymers: PEI–HZ–DOX (PHD) and PEI-PEG-Folate (PPF) with siRNA. The PHD, a conjugate of PEI (polyethylenimine) with doxorubicin (DOX) via a pH-responsive hydrazone linkage, enables pH-controlled drug release. The PPF, a tumor-targeting folate ligand conjugated to PEI using polyethyleneglycol (PEG) as a linker, enables immune evasion and cell-specific targeting. The prefunctionalized PHD and PPF as well as the self-assembly complexes reveals advantage on safety in further application for siRNA delivery. By exploiting distinct triple ratios of PHD, PPF and siRNA during nanocomplexes formulation, the folate surface density, DOX loading amount and siRNA complexation can be precisely and reproducibly changed. The studies showed that the complexes was capable of delivering siRNA and DOX to cancerous cells and release synchronously in cell by acid-triggered manner, i.e. hydrazone bond cleavage and endosome/lysosome escape using flow cytometry and confocal laser scanning microscopy analysis. The results highlight the potential for therapeutic gene silencing in vitro and in vivo using RT-PCR and non-invasive in vivo imaging systems. The PHD/PPF/siRNA complexes can increase DOX and siRNA accumulation in cancerous cells and decrease the nonspecific distribution in normal tissues by the combination of EPR effect of nanocarriers, pH-triggered drug release, folate-mediated targeted delivery, and synergistic action of DOX and siRNA.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomaterials - Volume 34, Issue 20, July 2013, Pages 4849–4859
نویسندگان
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