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Chemopreventive and therapeutic activity of combined complex nanoparticles with paclitaxel and sulforaphane for breast cancer (BaoU20MEDSF)

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  • Full or part time
    Dr Y Bao
    Prof D Pshezhetskiy
  • Application Deadline
    No more applications being accepted
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Paclitaxel chemotherapy is offered as part of both first and second line regimens for locally advanced or metastatic breast cancer. It is specifically offered for patients with aggressive triple negative breast cancer, however, a vast majority of these patients develop chemoresistance.

Recently, we and others have shown that mTOR inhibitors such as everolimus provide synergy in combination with taxane therapy in several solid tumours including breast PMID: 28615679 PMID: 27821815. A dietary isothiocyanate sulforaphane has been shown to inhibit proliferation and invasive activity of everolimus-resistant kidney cancer cells and demonstrated to be an mTOR inhibitor. Using cell and mouse models of prostate and breast cancer we have recently shown that polymer nanoparticles allow targeted therapy delivery to tumours leading to increased efficacy and reduced toxicity (PMID: 28724986 PMID: 28695300).

In this PhD project, we will perform synthesis and characterisation of complex nanoparticles (NPs) containing paclitaxel and sulforaphane. We will start by evaluating the complex NPs uptake by breast cancer cells using in vitro systems (2D and 3D) representing tumour microenvironment such as cancer cell-macrophages co-culture systems.

The anti-cancer activities of complex NPs will be evaluated using biological assays to measure cell proliferation, migration/invasion, clonogenicity apoptosis/autophagy and angiogenesis.

Finally, the anti-cancer effect and therapeutical potential of synthesised nanoparticles will be further investigated using a mouse breast cancer model powered by small animal imaging. The data obtained will help to translate this study to clinical trials, and the results will be published in high-impact journals.

For more information on the supervisor for this project, please go here:

This is a PhD programme.

The start date of the project is 1 October 2020.

The mode of study is full-time. The studentship length is 3 years.

Entry requirements:

Acceptable first degree in subject areas including Biochemistry, Cell/Molecular Biology, Cancer Biology/Oncology, and Nanosciences.

The standard minimum entry requirement is 2:1

Funding Notes

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at http://www.uea.ac.uk/study/postgraduate/research-degrees/fees-and-funding.

A bench fee may also be payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.

References

i) Zhang Y et al., The isothiocyanate sulforaphane inhibits mTOR in an NRF2-independent manner. Phytomedicine. 2019. doi.org/10.1016/j.phymed.2019.153062

ii) Campone, M. et al. Safety and pharmacokinetics of paclitaxel and the oral mTOR inhibitor everolimus in advanced solid tumours. Br J Cancer 2009; 100,315-321, doi:10.1038/sj.bjc.6604851.

iii) Wang Q, Alshaker H, Böhler T, Srivats S, Chao Y, Cooper C, Pchejetski D. Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer. Sci Rep. 2017;7(1):5901. doi:10.1038/s41598-017-06142-x.

iv) Xu Y, Han X, Li Y, Min H, Zhao X, Zhang Y, Qi Y, Shi Y, Qi S, Bao Y, Nie G. Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity. ACS Nano, 2019;13(11):13445-13455. doi: 10.1021/acsnano.9b07032

v) Alshaker H, Wang Q, Srivats S, Chao Y, Cooper C, Pchejetski D. New FTY720-Docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia and inhibits metastatic breast tumour growth. Breast Cancer Res Treat, 2017;10(10): p. 017-4380.



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