The doctoral dissertation in the field of Applied Physics will be examined at the Faculty of Science, Forestry and Technology, Kuopio campus.
What is the topic of your doctoral research? Why is it important to study the topic?
The topic of my doctoral research is photothermal therapy with black porous silicon nanoparticles for targeted cancer treatment. Nanoparticles (NPs) with high optical absorbance can generate heat under light irradiation, cause local hyperthermia, and ablate cancer cells resulting in effective photothermal therapy (PTT).
Compared to traditional chemo- and immunotherapies, which suffer from adverse side effects and lack tumor-targeting ability, NP-based PTT can overcome these limitations. NPs accumulate in tumor through passive targeting and targeting can be improved with targeting ligands or by coating NPs with cancer cell membrane.
In the present thesis, black porous silicon (BPSi) NPs are utilized as they have several advantageous properties, such as good biocompatibility, easily modified surface, and high photothermal conversion efficiency, that makes BPSi a good choice for PTT. The general aim is to develop a drug-free PTT approach using BPSi NPs for targeted cancer treatment.
What are the key findings or observations of your doctoral research?
In the first study, the biodistribution of BPSi NPs was studied systemically in vivo. The results indicated that BPSi NPs could efficiently accumulate into tumor via passive targeting approach.
In the second study, BPSi NPs were utilized in PTT and the concept of thermal isoeffect dose (TID) was used to evaluate the outcomes of NP-based PTT. The critical TID to induce significant cytotoxicity in cancer cells was discovered to be 70 min. Above this value, the cells started to undergo apoptosis. Thus, TID was proposed as a new tool to evaluate NP-based PTT.
In the last study, cell membrane coated BPSi NPs were utilized for active tumor-targeting PTT in vivo. It was shown that by tuning temperature, PTT was able to induce immunogenic cell death (ICD) and regulate MYC for cancer immunotherapy. Compared to lower (46 °C) or higher (54 °C) temperature PTT, PTT at 50 °C was the optimal condition to induce ICD and inhibit tumor growth.
Furthermore, MYC was downregulated at 50 °C, while upregulated at 46 °C. Thus, it was proven that PTT at 50 °C was optimal for cancer immunotherapy. With an in-depth understanding of the mechanism involved in PTT-triggered immunotherapy, the present thesis provides new insights for the development of more efficient BPSi NP-based PTT approaches for targeted cancer treatment in future.
What are the key research methods and materials used in your doctoral research?
I did my doctoral research in the Pharmaceutical Physics group, Department of Technical Physics. BPSi NPs were prepared and their physicochemical properties such as NP size, surface charge, and surface modifications were studied using dynamic light scattering, electron microscopy, thermogravimetry, and Fourier transform infrared spectroscopy.
Safety of NPs was studied measuring cell viability based on luminescence and NPs’ targeting was studied using fluorescence microscopy. Immunogenic cell death after PTT was studied imaging the cells expressing fluorescent HMGB1 and calreticulin proteins.
Moreover, the expression of MYC was studied using Western blot. In animal experiments, mice were given an intravenous injection of BPSi NPs and irradiated using laser to study the effect of PTT to inhibit tumor growth and activate immune response.
The doctoral dissertation of Emilia Happonen, MSc, entitled Photothermal therapy with black porous silicon nanoparticles for targeted cancer treatment will be examined at the Faculty of Science, Forestry and Technology, Kuopio Campus. The opponent will be Associate Professor Sabine van Rijt, Maastricht University, and the custos will be Adjunct Professor, Wujun Xu, University of Eastern Finland. Language of the public defence is English.
For more information, please contact:
Emilia Happonen, emilia.happonen@uef.fi
