Cancer targeting potential of folate targeted nanocarrier under comparative influence of tretinoin and dexamethasone.
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 (1)H-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.
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar 470003, India. jnarendr@yahoo.co.in
Raghvendra Singh
RS
Dhakad
Rakesh Kumar
RK
Tekade
Narendra Kumar
NK
Jain
D002470:Cell Survival / Q000187:drug effects; D050091:Dendrimers / Q000008:administration & dosage* / Q000737:chemistry; D003907:Dexamethasone / Q000008:administration & dosage* / Q000737:chemistry; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D058973:Folate Receptors, GPI-Anchored / Q000819:agonists / Q000378:metabolism*; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry; D006461:Hemolysis; D006801:Humans; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011126:Polypropylenes / Q000737:chemistry; D014212:Tretinoin / Q000008:administration & dosage* / Q000737:chemistry
D050091:Dendrimers; D058973:Folate Receptors, GPI-Anchored; D011126:Polypropylenes; C443641:poly(propyleneimine); D014212:Tretinoin; D003907:Dexamethasone; D005492:Folic Acid