Please use this identifier to cite or link to this item: http://dlib.scu.ac.ir/handle/2123/20894
Title: LHRH-Receptor Mediated Targeting of Cancer Cells Using Curcumin Nano-micelle Formulation
subject: LHRH;TNBC;cancer;nano-micelles;curcumin
Publisher: University of Sydney
Faculty of Medicine and Health
School of Pharmacy
Description: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among Australian women despite existing progress in the development of novel therapeutic strategies. Triple-negative breast cancer (TNBC), accounting for 10-17% of all breast carcinomas, represents an important clinical challenge in therapeutic demand. In this project, we fabricated, characterized and biologically evaluated nanoparticles (NPs) loaded with curcumin. We prepared curcumin-loaded nano-micelles with and without peptide conjugation. The [k6]LHRH-curcumin-NPs ([k6]LHRH-Cur-NPs), [k6(Ahx)]LHRH-curcumin-NPs ([k6(Ahx)]LHRH-Cur-NPs) and curcumin-NPs (Cur-NPs) were formulated. The conjugation of the peptides with the carboxylated F127 (F127-COOH) was confirmed by FTIR and MALDI-TOF. The Entrapment efficiency (EE%) and loading capacity (LC%) were determined by HPLC. EE% for all three NPs was found to be around 90%. LC% was found to be 8.9%, 7% and 5.7% for [k6]LHRH-Cur-NPs, [k6(Ahx)]LHRH-Cur-NPs and Cur-NPs respectively. Western blot analysis confirmed the presence of LHRH-R on MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines. IC50 values showed significantly enhanced antiproliferative activity for [k6(Ahx)]LHRH-Cur-NPs and [k6]LHRH-Cur-NPs as compared with Cur-NPs in all cell lines. The Time-lapse image analysis proved the enhanced uptake of nano-micelles compared to raw curcumin using IncuCyte® S3 over two days. The same experiment also demonstrated the LHRH-Cur-NPs proved to be more cytotoxic than the Cur-NPs alone and raw curcumin. The cellular internalization of [k6]LHRH-Cur-NPs, [k6(Ahx)]LHRH-Cur-NPs and Cur-NPs by the TNBC cell line, MDA-MB-231, proved enhanced uptake of LHRH-Cur-NPs compared to Cur-NPs and raw curcumin using Confocal Laser Scanning Microscope. Our current studies suggest that this advanced formulation is a promising strategy to overcome hurdles associated with the use of curcumin as a targeted therapy for TNBC cells via LHRH receptors.
Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.
URI: https://ses.library.usyd.edu.au/handle/2123/20894
More Information: http://hdl.handle.net/2123/20894
Appears in Collections:Postgraduate Theses

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Title: LHRH-Receptor Mediated Targeting of Cancer Cells Using Curcumin Nano-micelle Formulation
subject: LHRH;TNBC;cancer;nano-micelles;curcumin
Publisher: University of Sydney
Faculty of Medicine and Health
School of Pharmacy
Description: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among Australian women despite existing progress in the development of novel therapeutic strategies. Triple-negative breast cancer (TNBC), accounting for 10-17% of all breast carcinomas, represents an important clinical challenge in therapeutic demand. In this project, we fabricated, characterized and biologically evaluated nanoparticles (NPs) loaded with curcumin. We prepared curcumin-loaded nano-micelles with and without peptide conjugation. The [k6]LHRH-curcumin-NPs ([k6]LHRH-Cur-NPs), [k6(Ahx)]LHRH-curcumin-NPs ([k6(Ahx)]LHRH-Cur-NPs) and curcumin-NPs (Cur-NPs) were formulated. The conjugation of the peptides with the carboxylated F127 (F127-COOH) was confirmed by FTIR and MALDI-TOF. The Entrapment efficiency (EE%) and loading capacity (LC%) were determined by HPLC. EE% for all three NPs was found to be around 90%. LC% was found to be 8.9%, 7% and 5.7% for [k6]LHRH-Cur-NPs, [k6(Ahx)]LHRH-Cur-NPs and Cur-NPs respectively. Western blot analysis confirmed the presence of LHRH-R on MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines. IC50 values showed significantly enhanced antiproliferative activity for [k6(Ahx)]LHRH-Cur-NPs and [k6]LHRH-Cur-NPs as compared with Cur-NPs in all cell lines. The Time-lapse image analysis proved the enhanced uptake of nano-micelles compared to raw curcumin using IncuCyte® S3 over two days. The same experiment also demonstrated the LHRH-Cur-NPs proved to be more cytotoxic than the Cur-NPs alone and raw curcumin. The cellular internalization of [k6]LHRH-Cur-NPs, [k6(Ahx)]LHRH-Cur-NPs and Cur-NPs by the TNBC cell line, MDA-MB-231, proved enhanced uptake of LHRH-Cur-NPs compared to Cur-NPs and raw curcumin using Confocal Laser Scanning Microscope. Our current studies suggest that this advanced formulation is a promising strategy to overcome hurdles associated with the use of curcumin as a targeted therapy for TNBC cells via LHRH receptors.
Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.
URI: https://ses.library.usyd.edu.au/handle/2123/20894
More Information: http://hdl.handle.net/2123/20894
Appears in Collections:Postgraduate Theses

Files in This Item:
Click on the URI links for accessing contents.
Title: LHRH-Receptor Mediated Targeting of Cancer Cells Using Curcumin Nano-micelle Formulation
subject: LHRH;TNBC;cancer;nano-micelles;curcumin
Publisher: University of Sydney
Faculty of Medicine and Health
School of Pharmacy
Description: Breast cancer is the most common malignancy and the second leading cause of cancer-related death among Australian women despite existing progress in the development of novel therapeutic strategies. Triple-negative breast cancer (TNBC), accounting for 10-17% of all breast carcinomas, represents an important clinical challenge in therapeutic demand. In this project, we fabricated, characterized and biologically evaluated nanoparticles (NPs) loaded with curcumin. We prepared curcumin-loaded nano-micelles with and without peptide conjugation. The [k6]LHRH-curcumin-NPs ([k6]LHRH-Cur-NPs), [k6(Ahx)]LHRH-curcumin-NPs ([k6(Ahx)]LHRH-Cur-NPs) and curcumin-NPs (Cur-NPs) were formulated. The conjugation of the peptides with the carboxylated F127 (F127-COOH) was confirmed by FTIR and MALDI-TOF. The Entrapment efficiency (EE%) and loading capacity (LC%) were determined by HPLC. EE% for all three NPs was found to be around 90%. LC% was found to be 8.9%, 7% and 5.7% for [k6]LHRH-Cur-NPs, [k6(Ahx)]LHRH-Cur-NPs and Cur-NPs respectively. Western blot analysis confirmed the presence of LHRH-R on MCF-7, MDA-MB-231 and SK-BR-3 breast cancer cell lines. IC50 values showed significantly enhanced antiproliferative activity for [k6(Ahx)]LHRH-Cur-NPs and [k6]LHRH-Cur-NPs as compared with Cur-NPs in all cell lines. The Time-lapse image analysis proved the enhanced uptake of nano-micelles compared to raw curcumin using IncuCyte® S3 over two days. The same experiment also demonstrated the LHRH-Cur-NPs proved to be more cytotoxic than the Cur-NPs alone and raw curcumin. The cellular internalization of [k6]LHRH-Cur-NPs, [k6(Ahx)]LHRH-Cur-NPs and Cur-NPs by the TNBC cell line, MDA-MB-231, proved enhanced uptake of LHRH-Cur-NPs compared to Cur-NPs and raw curcumin using Confocal Laser Scanning Microscope. Our current studies suggest that this advanced formulation is a promising strategy to overcome hurdles associated with the use of curcumin as a targeted therapy for TNBC cells via LHRH receptors.
Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.
URI: https://ses.library.usyd.edu.au/handle/2123/20894
More Information: http://hdl.handle.net/2123/20894
Appears in Collections:Postgraduate Theses

Files in This Item:
Click on the URI links for accessing contents.