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Synthesis of smart carriers based on tryptophan-functionalized magnetic nanoparticles and its application in 5-fluorouracil delivery.

Mohammad Asadi TokmedashElham Seyyedi ZadehElham Nezami BalouchiZeinab SalehiMehdi Shafiee Ardestani
Published in: Biomedical materials (Bristol, England) (2022)
Multifunctional nanocarriers, specifically for tumor targeting and traceable features, have been increasingly considered in cancer therapies. Herein, a novel targeting agent (TA), tryptophan (TRP), was proposed for the synthesis of functionalized (3-aminopropyl) triethoxysilane-iron oxide nanoparticles using two methods, creating a smart drug delivery system (DDS). In one method, two-step, glutaraldehyde (GA) as a linker, bonded TRP and amino-functionalized magnetite, and in the second method, one step, TRP binding was carried out by (3-dimethyl aminopropyl)-N'-ethyl carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide ester. The synthesis yield of the second method was 7% higher than the first method. After synthesizing DDS, 5-fluorouracil (5-FU) was loaded on nanocarriers and was observed TRP functionalized nanoparticles by GA have better loading efficiency, which was 50% greater than the product from the one-step method. A pH-sensitive release profile was also studied for 5-FU/DDS with the release of almost 75% and 50% at pH 5.5 and 7.4, respectively. To analyze the biological aspects of nanocarriers, human breast cancer, MCF-7, and embryonic kidney, HEK293, cell lines were used for cellular uptake and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. In vitro studies confirmed that TRP can act as a TA as its cellular uptake through cancerous cells was 40% greater than normal cells, and the MTT assay confirmed that using DDS can increase and decrease the cell viability of normal cells and cancerous cells, respectively, compared to free drug. Therefore, it was concluded that advanced nano-assembly is a great candidate for breast cancer cell-targeted delivery.
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