Document Type

Thesis

Degree Name

Master of Science (MSc)

Department

Health Science

Program Name/Specialization

<--Please Select Program Name/Specialization-->

Faculty/School

Faculty of Science

First Advisor

Nirosha J. Murugan

Advisor Role

Principle Investigator, Thesis Supervisor, Thesis Committee Member

Second Advisor

Nicolas Rouleau

Advisor Role

Thesis Committee Member, Co-Thesis Supervisor

Third Advisor

Sarah Poynter

Advisor Role

Thesis Committee Member

Abstract

The rate of resistance to immune checkpoint inhibitor treatment in metastatic melanoma is quite high, with an overall rate of 70%. Melanoma achieves these high rates of resistance by suppressing the immune response in the tumour microenvironment (TME), making them immunologically “cold”. The type 1 interferon response could be leveraged to initiate immune responses in melanoma, making their “cold” TMEs “warm” again. Double-stranded ribonucleic acids (dsRNAs) are potent activators of an innate immune response; however, they are susceptible to degradation by nucleases present in the body and need a carrier. Silk nanoparticles (SNPs) are an ideal drug-delivery platform as they are made from a non-antigenic biomaterial and can protect PIC from nucleases via steric inhibition. In this study, dsRNA-SNP complexes are synthesized and optimized for stability and delivery of PIC, a synthetic non-coding dsRNA molecule. The resulting cationic particle complexes had favourable physicochemical properties with respective size, PDI, and zeta-potentials of 159.83 ± 18.65nm, 0.21 ± 0.02, and 33.11 ± 1.08mV. Using an in-vitro B16F10 mouse melanoma model, their cytotoxic and immunostimulatory effects were investigated. Results show stable non-cytotoxic SNP complexes that conferred protection to PIC from nucleases present in the media. However, their immunostimulatory potential remains uncertain and warrants further investigation, as the release of PIC from the complexes may be tunable by modulating the complex zeta-potential, leading to faster responses.

Convocation Year

2026

Convocation Season

Spring

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