Multimodal nano-theranostic systems targeting tumour biomarkers

Young, Richard (2019). Multimodal nano-theranostic systems targeting tumour biomarkers. University of Birmingham. Ph.D.

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Abstract

Folate receptor overexpression is a confirmed cancer biomarker which has been relatively underutilised within the literature in the application of targeted cellular delivery of therapeutics and diagnostics to date.

A folate receptor targeting theranostic nanoparticle system has been developed and its ability to track nanoparticle uptake and deliver a novel Pt(IV) pro drug to human cancer cell lines measured. This system comprises folate capped gold nanoparticles for the targeted delivery of a fluourescent ruthenium based polypyridyl probe and a novel Pt(IV) pro drug to folate receptor positive cell lines. The ability of the system to display selective uptake in folate receptor positive cell lines was probed through comparative uptake of a citrate capped gold nanoparticle system, comprising the same theranostic agents as that of the folate capped system. This difference in uptake was investigated through the use of folate receptor blocking and simulating flow of particles within a cellular suspension, comparing uptake of respective particles with confocal microscopy, flow cytometry and ICPMS.

The novel Pt(IV) agent has been fully characterised and its anti-cancer efficacy investigated, presenting with improved toxicity over cisplatin in cisplatin resistant A549 cells. Cisplatin-DNA adducts have been identified through employment of a commercially available antibody, where the Pt(IV) agent displayed increased adducts over cisplatin alone. This adduct formation and imparted toxicity was investigated by confocal microscopy, flow cytometry, ICPMS and MTT assays in A549 cells.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):