انتقال هدفمند داروی السکلومول به سلول های سرطانی روده بزرگ با سامانه حمل دارویی هدفمند سیلیکا میان تخلخل مغناطیسی

محورهای موضوعی : شیمی آلی

مجتبی تارین ¹ , مریم بابایی ² , حسین عشقی ³ , مریم مقدم متین ⁴ , امیر شکوه سلجوقی ⁵

1 - دانشجوی دکترای گروه شیمی، دانشکده علوم، دانشگاه فردوسی مشهد، مشهد، ایران.
2 - دکترای شیمی آلی، گروه شیمی، دانشکده علوم، دانشگاه فردوسی مشهد، مشهد، ایران.
3 - استاد شیمی آلی، گروه شیمی، دانشکده علوم، دانشگاه فردوسی مشهد، مشهد، ایران.
4 - استاد زیست شناسی، گروه زیست شناسی، دانشکده علوم، دانشگاه فردوسی مشهد، مشهد، ایران.
5 - دانشیار شیمی معدنی، گروه شیمی، دانشکده علوم، دانشگاه فردوسی مشهد، مشهد، ایران.

تاریخ دریافت : 1402/02/25 تاریخ پذیرش : 1402/04/13 تاریخ انتشار : 1402/09/01

کلید واژه: دارورسانی هدفمند, سرطان روده بزرگ, السکلومول, نانوذره‌های میان(مزو)تخلخل سیلیکا, واپایش رهایش دارو,

چکیده مقاله :

در این پژوهش، انتقال هدفمند داروی پادسرطانی السکلومول به سلول های سرطانی روده بزرگ از راه گسترش نانوذره های میان(مزو)تخلخل سیلیکای مغناطیسی (MMSNs) و پیوند عامل های متفاوت مانند واپایش گرهای دریچه ای طلا، بسپار پلی اتیلن گلیکول (PEG) دوعاملی و آپتامر مربوط به مولکول های چسبنده سطح سلول های اپی تلیالی (EpCAM) به سطح نانوحامل صورت گرفت. پس از سنتز سامانه حمل دارویی، ویژگی های فیزیکی-شیمیایی آن ارزیابی شدند. همچنین، ویژگی پادسرطانی داروی السکلومول و سامانه حمل دارویی با لیگاند ویژه آپتامر EpCAM و بدون آن در شرایط برون تنی مقایسه شد. بررسی تصویرهای میکروسکوپ الکترونی نشان داد که نانوذره های MMSNs کروی با قطر حدود 19 نانومتر بودند. السکلومول با موفقیت در حفره های باز این نانوذره ها بارگذاری شد و درصد بارگذاری حدود 39 درصد تخمین زده شد. همچنین، پس از فرایند درپوش گذاری و مسدوسازی حفره ها، نانوذره های Au-ELC-MMSN-NH2 در طی 96 ساعت، رهایش پیوسته و وابسته به pH نشان دادند. نتیجه هایMTT نشان داد که این نانوذره ها سمیت چشمگیری را در برابر سلول های سرطانی روده بزرگ و بیان کننده گیرنده EpCAM در مقایسه با سلول های CHO اعمال می کنند. با توجه به نتیجه های امیدوارکننده APT-PEG-Au-ELC-MMSN-NH2، سامانه تهیه شده می تواند به عنوان جایگزین درمانی السلکومول برای سرطان روده بزرگ استفاده شود. هرچند، پیش از استفاده گسترده آن در حوزه بالینی، به آزمایش های بیشتری نیاز است.

چکیده انگلیسی:

In this research, the targeted delivery of elesclomol to colorectal cancer cells was explored through the development of magnetic mesoporous silica nanoparticles (MMSNs) loaded with elesclomol and surface modification with gold gatekeepers, bifunctional polyethylene glycol (PEG) polymer, and epithelial cell adhesion molecule (EpCAM) aptamers to improve drug delivery performance. The physicochemical properties of nanocarriers were characterized and the cellular toxicity of elesclomol, and nano-delivery system with and without EpCAM aptamer modification has been investigated in vitro. High resolution transmission electron microscopy (HRTEM) and field emission scanning electron microscopy (FESEM) showed that MMSNs had a uniform spherical morphology with a diameter of 19 nm and a negative surface charge. Elesclomol was successfully encapsulated in the open porous structure of the nanocarrier. The encapsulation efficiency (EE) and drug loading capacity (LC) were about 88% and 39%, respectively. Moreover, the prepared Au-ELC-MMSN-NH2 displayed pH responsive and sustained drug release within 96 h. Targeted nano-delivery systems were prepared with a final diameter of 89 nm and a negative surface charge. The MTT assay revealed that the targeted nano-delivery system induced highly effective cytotoxicity on colorectal cancer cells-expressing EpCAM aptamer (HT-29) compared to the CHO cells. This engineered nano-platform is a promising elesclomol replacement therapy for colorectal cancer. However, further experiments are required before it can be practiced in the clinic.

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