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Title: Active targeting of cancer cells using gemcitabine conjugated platinum nanoparticles
Authors: Odayar, Kriya 
Issue Date: 2017
Nanotechnology is explained as the science of engineered materials and systems on a molecular scale. This innovation is currently used in a wide variety of applications which include using these nanoparticles as drug delivery vehicles. Such nanocarriers are relatively smaller than 100 nm in size with the ability to convey therapeutic drugs to a number of disease sites.

Platinum-based nanoparticles have been extensively used in a number of applications namely catalysts, gas sensors, glucose sensors and cancer therapy. The properties of platinum nanoparticles (PtNP’s) typically depend on characteristics such as shape, particle size, elemental composition and structure, all of which can be manipulated and controlled in the fabrication process. Their unique size in the nanometer scale makes platinum nanoparticles an ideal candidate as targeted drug delivery vehicles.

To target an anticancer drug to a diseased site is a distinctive feature of most studies, which aim to transfer an adequate dosage of the drug to cancer cells. Transport systems used as carriers of anticancer drugs offer numerous advantages, which include improved efficacy and a decrease in toxicity towards healthy cells when compared to standard drugs.

The aim of this study was to determine the effect of platinum nanoparticles, gemcitabine and gemcitabine conjugated platinum nanoparticles (Hybrids) against cancer cells and healthy cells and to determine the mode of cell death and cell death pathways using flow cytometry.

Platinum nanoparticles were synthesized via the reduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. Synthesized platinum nanoparticles and the hybrids were characterized by observing peaks at 301 nm and 379 nm respectively using UV-visible spectroscopy.

TEM images revealed that the PtNP’s and the conjugate compounds were spherical in shape with core sizes of 1.14 nm - 1.65 nm and 1.53 - 2.66 nm respectively. The bioactivity platinum nanoparticles, gemcitabine and the hybrids were investigated using MCF7 and Melanoma cancer cells at different concentrations from 0.10 to 100 µg/ml.

Results indicated that conjugated nanoparticles induced the highest cell inhibition against both cell lines compared to gemcitabine and platinum nanoparticles. Bioactivity against PBMC (peripheral blood mononuclear) cells indicated that all three compounds show little or no effect towards the healthy cell line compared to the control.

Melanoma cell line was used to determine the mode of cell death. Apoptosis was detected using Annexin V-FITC to detect membrane changes, JC-1 to detect a loss in mitochondrial membrane potential and caspase-3 assay kits. Results indicated that a significant amount of cell death was caused by cleavage of caspase-3.

Nanoparticle drug delivery is an area that has shown significant promise in cancer treatment. Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates.

Imagine, something that is atleast or more than 80,000 times smaller than the edge of the ridge on a fingertip and unlocks a new wilderness into cancer research. Nanotechnology, known as the science of minute, is changing the approach to cancer and especially future diagnosis and treatment.

Nanotechnology permits scientists to fabricate new apparatuses that are definitely smaller than cells, giving them the chance to attack tumor diseased cells. This innovation not just empowers practitioners to recognize malignancies prior but additionally holds the guarantee of halting cancer growth before it further develops. This progressive approach is so exact, specialists will in future be able to outline a unique treatment for an individual’s own restorative and hereditary profile.

Researchers are designing nanoparticles that detect and destroy diseased cells and this optimistic innovation could be personalized for targeted drug delivery, enhanced imaging and ongoing affirmation of cancer cell death.

The National Cancer Institute remains hopeful that facilitated development, nanotechnology will drastically change cancer treatment.
Submitted in fulfilment of the requirements of the Degree of Master's in Biotechnology, Durban University of Technology, Durban, South Africa, 2017.
Appears in Collections:Theses and dissertations (Applied Sciences)

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