چاپ صفحه |  صفحه نخست سامانه |  نویسندگان |  اطلاعات تفضیلی |  دانلود مقاله | دانشگاه علوم پزشکی تبریز |
| نویسنده | نفر چندم مقاله |
|---|---|
| حسین محمودی | اول |
| رعنا جهانبان اسفهلان | دوم |
| عنوان | متن |
|---|---|
| خلاصه مقاله | We report on design and synthesis of novel hypoxia responsive nanoparticles (HRNP) composed of methoxy polyethylene glycol - 4,4 dicarboxylic azolinker-chitosan (mPEG-Azo-chitosan) as ideal drug delivery platform for Fingolimod (FTY720) delivery to achieve selective and highly enhanced TNBC treatment efficacy. We formulated HRNP with a size of 49.86 nm and a zeta potential of +3.22 mV, which after PEG shedding can shift into a positively-charged chitosan nanoparticle (+30.3 mV), possessing self-activation ability under hypoxia situation in vitro, 2D and 3D culture. This capability causes deep penetration into the tumor with targeted drug delivery and achieving significant anti-cancer effects to completely inhibit the growth of invasive TNBC microtumors. Treatment with lower doses of Fingolimod (10 μg) significantly reduced MDA-MB-231 microtumor size to 15% and induced apoptosis by 88% within 72 hours after single-dose treatment. Plus, HRNP@F was capable of superior shrinkage of 4T1 tumors in mice compared to control and free drug in absence of any side effects. To the best of our knowledge this is the first report on formulation of novel hypoxia-responsive chitosan nanoparticles with desirable physicochemical properties, rapid and selective self-activation potential to generate highly-charged nanosized tumor-penetrating chitosan NPs. This formulation is capable of targeting both proximal and distant located tumor cells, enabling efficient eradication of hard-to-hit hypoxic solid tumors. |
| کلمات کلیدی | Chitosan nanoparticles; tumor microenvironment; hypoxia responsive; Fingolimod; TNBC breast cancer therapy |
| نام فایل | تاریخ درج فایل | اندازه فایل | دانلود |
|---|---|---|---|
| Mahmudi abstract.docx | 1403/09/19 | 529957 | دانلود |
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