Cancer Targeting Potential of Folate Targeted Nanocarrier under Comparative Influence of Tretinoin and Dexamethasone
Cancer Targeting Potential of Folate Targeted Nanocarrier under Comparative Influence of Tretinoin and Dexamethasone
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DOI：
10.2174/1567201811310040012
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发表时间：
2013-08-01
影响因子：
2.4
通讯作者：
Jain, Narendra Kumar
中科院分区：
文献类型：
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作者：
Dhakad, Raghvendra Singh;Tekade, Rakesh Kumar;Jain, Narendra Kumar
本研究的目的是探索叶酸偶联树枝状聚合物（聚丙烯亚胺，PPI）在叶酸受体上调剂（全反式维甲酸，ATRA和地塞米松，DEXA）的策略影响下的癌症靶向潜力。合成了叶酸偶联的树枝状大分子纳米偶联物（FPPI），并用FTIR和1H-1 NMR对其进行了表征.对MCF-7细胞进行细胞系研究。ATRA和DEXA预处理48 h后，叶酸受体选择性上调分别为对照组的2.17倍和1.65倍。ATRA对叶酸受体表达的上调作用比DEXA高50.47 ± 2.11%。这两种上调剂在上调叶酸受体时显示出12 h的滞后期。48小时后，发现裸多西他赛（DTX）和负载DTX的树枝状聚合物（PPI-DTX）的IC 50值分别为678.93 +/- 11.99 nM和663.51 +/- 15.23 nM，而负载DTX的叶酸锚定树枝状聚合物（FPPI-DTX）显示出选择性降低的IC 50值468.56 +/- 20.86 nM。FPPI-DTX进一步显示在ATRA和DEXA预处理的细胞中IC 50值的显著降低，其中观察到的IC 50值分别为184.21 nM和290.40 +/- 14.05 nM。该研究还得出结论，与DEXA相比，ATRA是一种上级受体上调剂以及基于叶酸的靶向促进剂。
The objective of this investigation was aimed to explore the cancer targeting potential of folate conjugated dendrimer (polypropylene imine, PPI) under strategic influence of folate receptor up-regulators (all trans Retinoic acid, ATRA and Dexamethasone, DEXA). The folate conjugated dendrimer nanoconjugate (FPPI) was synthesized and characterized by FTIR, and H-1-NMR spectroscopy. The cell line studies investigations were performed on MCF-7 cells. ATRA and DEXA caused 2.17 and 1.65 folds selective up-regulation of folate receptor respectively, when compared with untreated control, after 48 h of pretreatment. ATRA caused 50.47 +/- 2.11% more up regulation of folate receptor, than DEXA treated cell. Both up regulators showed a lag phase of 12 h in up-regulating the folate receptors. After 48 h, the IC50 values of naked docetaxel (DTX) and DTX loaded dendrimer (PPI-DTX) were found to be 678.93 +/- 11.99 nM and 663.51 +/- 15.23 nM, respectively, while DTX loaded folate-anchored dendrimer (FPPI-DTX) showed a selectively lowered IC50 value of 468.56 +/- 20.86 nM. FPPI-DTX further showed a significant reduction in IC50 value in ATRA and DEXA pretreated cells, wherein IC50 values of 184.21 nM and 290.40 +/- 14.05 nM, respectively were observed. The study also concludes ATRA to be a superior receptor up-regulator as well as promoter of folate based targeting compared to DEXA.