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• W2759576182 abstract "Cancer treatment using siRNA based therapies pose various limitations such as off-target effects and degradation due to lack of specific delivery in desired cells. The aim of the present study was to develop multifunctional targeted nanoconstructs, which can efficiently and precisely deliver siRNA and silence the desired gene of interest in various LHRH overexpressing cancer cells. Herein, we report the development of triblock, PAMAM-histidine-PEG dendritic nanoconstructs functionalized with triptorelin (an LHRH analog) for targeted siRNA delivery to LHRH overexpressing breast (MCF-7) and prostate (LNCaP) cancer cells. The nanoconstructs were characterized using 1H NMR and DLS and displayed a very low cationic charge to avoid off-target interactions. The developed nanoconstructs showed negligible cytotoxicity and hemolytic activity with efficient siRNA loading, excellent serum stability, and strongly protected siRNA from degradation. Further, confocal microscopy results confirmed extremely significant (p < 0.001) higher cellular uptake of cy5.5 conjugated targeted nanoparticles (NPs) in both cancer cell lines than nontargeted NPs. Also, targeted NPs specifically delivered cy3-tagged siRNA to MCF-7 cells. Co-localization studies in MCF-7 and LNCaP cells further established that targeted NPs traveled through the endolysosomal pathway and escaped endosomes within 6 h of incubation. Gene silencing studies in luciferase expressing MCF-7 and LNCaP cell lines demonstrated that the targeted NPs exhibited extremely significant (p < 0.001) silencing of luciferase gene. Additionally, receptor blockade studies further confirmed the specificity of targeted NPs and suggested that targeted NPs entered cancer cells via LHRH receptor mediated endocytosis, which was evident through insignificant gene silencing in receptor blocked cells. Thus, the results indicated that PAMAM-histidine-PEG-triptorelin could be a promising approach for siRNA delivery, gene silencing, and tumor therapy in all LHRH overexpressing cancer cells." @default.
• W2759576182 created "2017-10-06" @default.
• W2759576182 creator A5005427576 @default.
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• W2759576182 date "2017-10-09" @default.
• W2759576182 modified "2023-10-03" @default.
• W2759576182 title "Triptorelin Tethered Multifunctional PAMAM-Histidine-PEG Nanoconstructs Enable Specific Targeting and Efficient Gene Silencing in LHRH Overexpressing Cancer Cells" @default.
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• W2759576182 doi "https://doi.org/10.1021/acsami.7b11024" @default.
• W2759576182 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28949503" @default.
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