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[Excluded] [Excluded] Engineering of cell microenvironment-responsive polypeptide nanovehicle co-encapsulating a synergistic combination of small molecules for effective chemotherapy in solid tumors | |
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- ÃâÆÇ¿¬µµ: JAN 15 2017
[History] - 2018³â 8¿ù 13ÀÏ ÇöÀç HCP ¸®½ºÆ®¿¡¼ Á¦¿ÜµÇ¾î ÀÖ½À´Ï´Ù. - 7¿ù/8¿ù 2017³â ºÎ·Î, ÀÌ ÀÎ¿ë ºóµµ°¡ ³ôÀº ³í¹®ÀÇ Àοë Ƚ¼ö°¡ ºÐ¾ß¿Í ÃâÆÇ ¿¬µµ¿¡ ´ëÇØ Materials Science °ü·Ã Çмú ºÐ¾ß¿¡¼ »óÀ§ 1%¿¡ ¿Ã¶ú½À´Ï´Ù. [Abstract] In this study, we report a facile method to construct a bioactive (poly(phenylalanine)-b-poly(t-histidine)-b-poly(ethylene glycol) polypeptide nanoconstruct to co-load doxorubicin (DOX) and quercetin (QUR) (DQ-NV). The smart pH-sensitive nanovehicle was fabricated with precisely tailored drug-to-carrier ratio that resulted in accelerated, sequential drug release. As a result of ratiometric loading, QUR could significantly enhance the cytotoxic potential of DOX, induced marked cell apoptosis; change cell cycle patterns, inhibit the migratory capacity of sensitive and resistant cancer cells. In particular, pro-oxidant QUR from DQ-NV remarkably reduced the GSH/GSSG ratio, indicating high oxidative stress and damage to cellular components. DQ-NV induced tumor shrinkage more effectively than the single drugs in mice carrying subcutaneous SCC-7 xenografts. DQ-NV consistently induced high expression of caspase-3 and PARP and low expression of Ki67 and CD31 immunomarkers. In summary, we demonstrate the development of a robust polypeptide-based intracellular nanovehicle for synergistic delivery of DOX/QUR in cancer chemotherapy. |
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ÀÌÀü±Û | ±¹°¡¿¬±¸ºñ·Î ºÎ½ÇÇÐȸ Âü°¡ÇÑ 398¸í ÃâÀåºñ 14¾ï¿ø ȸ¼ö / ¸ÅÀÏ°æÁ¦ (2018.12.20.) |
´ÙÀ½±Û | ¿¬±¸ºñ Ⱦ·É Á¦Àç °È¡¦Àå±â°£ ¿¬±¸ Âü¿© Á¦ÇÑ / ¸ÅÀÏ°æÁ¦ (2018.12.19.) |
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