Please use this identifier to cite or link to this item: http://dlib.scu.ac.ir/handle/2123/13437
Title: Towards the Specific Targeting of Regions of Solid Tumours Remote to the Vasculature
subject: chemotherapy;platinum;tumour;selective targeting
Publisher: University of Sydney
Faculty of Science
Description: In order to examine the effectiveness of the carboxylic acid functional group at targeting tumour acidosis, four types of Pt(IV) complexes were synthesised and examined. The type one Pt(IV) complex had low pKa (3.5 and 4.4) and lacked lipophilicity. It exhibited negligible accumulation and growth inhibition in A2780 cells in both acidified and regular growth media. The type two Pt(IV) complex was significantly more lipophilic than the type one complex, but had similar pKa values. Whilst the accumulation of the type two complex was higher than that of type one complex, it was not pH dependent, indicating that aliphatic carboxylic acid moieties, such as the 3-carboxypropanoato ligand were not effective at influencing the celluar accumulation. The type three Pt(IV) complex was designed to have two 2-carboxybenzoato ligands at the axial coordination sites. As a result, its pKa (between 4.8 and 6.2) were found to be significantly higher than that of the type one and two complex. Although, the complex exhibited a three-fold selectivity at accumulating in cells in acidified medium over regular medium, it did not exhibit any cytotoxic effects. The type four complex had high lipophilicity as well as a 2-carboxybenzoate moiety. Its cellular accumulation was significantly higher than that of the type three complex, despite the lack of any selectivity based on pH. The diffusion of the Pt complexes through multicellular aggregates was also investigated in the current study. The type one Pt(IV) complex was found to localise in the central regions of the multicellular spheroid constructed from DLD-1 cells. The diffusion of the type one complex through multicellular layers was not able to be observed due to the interactions between the complex and the Teflon semi-permeable membrane. The diffusion of [PtIICl2en] through DLD-1 MCL was investigated using GF-AAS and the diffusion constants were found to be 6.16 × 10-8 cm2 sec-1, lower than reported values of 1.77 × 10-7 cm2 sec-1.
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/2123/13437
More Information: http://hdl.handle.net/2123/13437
Appears in Collections:Postgraduate Theses

Files in This Item:
Click on the URI links for accessing contents.
Title: Towards the Specific Targeting of Regions of Solid Tumours Remote to the Vasculature
subject: chemotherapy;platinum;tumour;selective targeting
Publisher: University of Sydney
Faculty of Science
Description: In order to examine the effectiveness of the carboxylic acid functional group at targeting tumour acidosis, four types of Pt(IV) complexes were synthesised and examined. The type one Pt(IV) complex had low pKa (3.5 and 4.4) and lacked lipophilicity. It exhibited negligible accumulation and growth inhibition in A2780 cells in both acidified and regular growth media. The type two Pt(IV) complex was significantly more lipophilic than the type one complex, but had similar pKa values. Whilst the accumulation of the type two complex was higher than that of type one complex, it was not pH dependent, indicating that aliphatic carboxylic acid moieties, such as the 3-carboxypropanoato ligand were not effective at influencing the celluar accumulation. The type three Pt(IV) complex was designed to have two 2-carboxybenzoato ligands at the axial coordination sites. As a result, its pKa (between 4.8 and 6.2) were found to be significantly higher than that of the type one and two complex. Although, the complex exhibited a three-fold selectivity at accumulating in cells in acidified medium over regular medium, it did not exhibit any cytotoxic effects. The type four complex had high lipophilicity as well as a 2-carboxybenzoate moiety. Its cellular accumulation was significantly higher than that of the type three complex, despite the lack of any selectivity based on pH. The diffusion of the Pt complexes through multicellular aggregates was also investigated in the current study. The type one Pt(IV) complex was found to localise in the central regions of the multicellular spheroid constructed from DLD-1 cells. The diffusion of the type one complex through multicellular layers was not able to be observed due to the interactions between the complex and the Teflon semi-permeable membrane. The diffusion of [PtIICl2en] through DLD-1 MCL was investigated using GF-AAS and the diffusion constants were found to be 6.16 × 10-8 cm2 sec-1, lower than reported values of 1.77 × 10-7 cm2 sec-1.
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/2123/13437
More Information: http://hdl.handle.net/2123/13437
Appears in Collections:Postgraduate Theses

Files in This Item:
Click on the URI links for accessing contents.
Title: Towards the Specific Targeting of Regions of Solid Tumours Remote to the Vasculature
subject: chemotherapy;platinum;tumour;selective targeting
Publisher: University of Sydney
Faculty of Science
Description: In order to examine the effectiveness of the carboxylic acid functional group at targeting tumour acidosis, four types of Pt(IV) complexes were synthesised and examined. The type one Pt(IV) complex had low pKa (3.5 and 4.4) and lacked lipophilicity. It exhibited negligible accumulation and growth inhibition in A2780 cells in both acidified and regular growth media. The type two Pt(IV) complex was significantly more lipophilic than the type one complex, but had similar pKa values. Whilst the accumulation of the type two complex was higher than that of type one complex, it was not pH dependent, indicating that aliphatic carboxylic acid moieties, such as the 3-carboxypropanoato ligand were not effective at influencing the celluar accumulation. The type three Pt(IV) complex was designed to have two 2-carboxybenzoato ligands at the axial coordination sites. As a result, its pKa (between 4.8 and 6.2) were found to be significantly higher than that of the type one and two complex. Although, the complex exhibited a three-fold selectivity at accumulating in cells in acidified medium over regular medium, it did not exhibit any cytotoxic effects. The type four complex had high lipophilicity as well as a 2-carboxybenzoate moiety. Its cellular accumulation was significantly higher than that of the type three complex, despite the lack of any selectivity based on pH. The diffusion of the Pt complexes through multicellular aggregates was also investigated in the current study. The type one Pt(IV) complex was found to localise in the central regions of the multicellular spheroid constructed from DLD-1 cells. The diffusion of the type one complex through multicellular layers was not able to be observed due to the interactions between the complex and the Teflon semi-permeable membrane. The diffusion of [PtIICl2en] through DLD-1 MCL was investigated using GF-AAS and the diffusion constants were found to be 6.16 × 10-8 cm2 sec-1, lower than reported values of 1.77 × 10-7 cm2 sec-1.
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/2123/13437
More Information: http://hdl.handle.net/2123/13437
Appears in Collections:Postgraduate Theses

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