Elham Ajorlou1,2,3, Ahmad Yari Khosroushahi4,5, Hamid Yeganeh6. 1. Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. 3. Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Tabriz University of Medical Sciences, Tabriz, Iran. 4. Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Yarikhosroushahia@tbzmed.ac.ir. 5. Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Daneshgah Street, Tabriz, Iran, P.O.Box 51664-14766. Yarikhosroushahia@tbzmed.ac.ir. 6. Polyurethanes Department Faculty of Polymer Science, Iran Polymer & Petrochemical Institute (IPPI), P.O.Box: 14965/115, Tehran, Iran. h.yeganeh@ippi.ac.ir.
Abstract
PURPOSE: Since the introduction of nanocarriers, the delivery of chemotherapeutic agents for treatment of patients with cancer has been possible with better effectiveness. The latest findings are also support that further enhancement in therapeutic effectiveness of these nanocarriers can be attained, if surface decoration with proper targeting agents is considered. METHODS: This study aimed at treating a variety of 4T1 murine breast cancer cell line, mainly demonstrating high folate and TRAIL receptor expression of cancerous cells. The therapeutic efficacy of paclitaxel loaded Cremophore EL (Taxol®), paclitaxel loaded waterborne polyurethane nanomicelles (PTX-PU) and paclitaxel loaded waterborne polyurethane nanomicelles conjugated with folate (PTX-PU-FA) and TRAIL (PTX-PU-TRAIL) on treating 4T1 cell was also compared. RESULTS: The findings that worth noting are: PTX-PU outperformed Taxol® in a Balb/C mouse model, furthermore, tumor growth was adequately curbed by folate and TRAIL-decorated nanomicelles rather than the unconjugated formulation. Tumors of mice treated with PTX-PU-FA and PTX-PU-TRAIL shrank substantially compared to those treated with Taxol®, PTX-PU and PTX-PU-TRAIL (average 573 mm(3) versus 2640, 846, 717 mm(3) respectively), 45 days subsequent to tumor inoculation. The microscopic study of hematoxylin-eosin stained tumors tissue and apoptotic cell fraction substantiated that the most successful therapeutic effects have been observed for the mice treated with PTX-PU-FA (about 90% in PTX-PU-FA versus 75%, 60%, 15% in PTX-PU-TRAIL, PTX-PU, and Taxol® group respectively). CONCLUSIONS: Using folate-targeted nanocarriers to treat cancers characterized by a high level of folate ligand expression is well substantiated by the findings of this study.
PURPOSE: Since the introduction of nanocarriers, the delivery of chemotherapeutic agents for treatment of patients with cancer has been possible with better effectiveness. The latest findings are also support that further enhancement in therapeutic effectiveness of these nanocarriers can be attained, if surface decoration with proper targeting agents is considered. METHODS: This study aimed at treating a variety of 4T1 murinebreast cancer cell line, mainly demonstrating high folate and TRAIL receptor expression of cancerous cells. The therapeutic efficacy of paclitaxel loaded Cremophore EL (Taxol®), paclitaxel loaded waterborne polyurethane nanomicelles (PTX-PU) and paclitaxel loaded waterborne polyurethane nanomicelles conjugated with folate (PTX-PU-FA) and TRAIL (PTX-PU-TRAIL) on treating 4T1 cell was also compared. RESULTS: The findings that worth noting are: PTX-PU outperformed Taxol® in a Balb/C mouse model, furthermore, tumor growth was adequately curbed by folate and TRAIL-decorated nanomicelles rather than the unconjugated formulation. Tumors of mice treated with PTX-PU-FA and PTX-PU-TRAIL shrank substantially compared to those treated with Taxol®, PTX-PU and PTX-PU-TRAIL (average 573 mm(3) versus 2640, 846, 717 mm(3) respectively), 45 days subsequent to tumor inoculation. The microscopic study of hematoxylin-eosin stained tumors tissue and apoptotic cell fraction substantiated that the most successful therapeutic effects have been observed for the mice treated with PTX-PU-FA (about 90% in PTX-PU-FA versus 75%, 60%, 15% in PTX-PU-TRAIL, PTX-PU, and Taxol® group respectively). CONCLUSIONS: Using folate-targeted nanocarriers to treat cancers characterized by a high level of folate ligand expression is well substantiated by the findings of this study.
Entities:
Keywords:
TRAIL; folate receptor; paclitaxel; targeting drug delivery
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