Abstract
Hyperthermia acts as a powerful adjuvant to radiation therapy and chemotherapy. Recent advances show that gold nanoparticles (Au-NPs) can mediate highly localized thermal effects upon interaction with laser radiation. The purpose of the present study was to investigate via in silico simulations the mechanisms of Au-NPs and microwave-induced hyperthermia, in correlation to predictions of tumor control (biological endpoints: tumor shrinkage and cell death) after hyperthermia treatment. We also study in detail the dependence of the size, shape and structure of the gold nanoparticles on their absorption efficiency, and provide general guidelines on how one could modify the absorption spectrum of the nanoparticles in order to meet the needs of specific applications. We calculated the hyperthermia effect using two types of Au-NPs and two types of spherical tumors (prostate and melanoma) with a radius of 3 mm. The plasmon peak for the 30 nm Si-core Au-coated NPs and the 20 nm Au-NPs was found at 590 nm and 540 nm, respectively. Considering the plasmon peaks and the distribution of NPs in the tumor tissue, the induced thermal profile was estimated for different intervals of time. Predictions of hyperthermic cell death were performed by adopting a three-state mathematical model, where “three-state” includes (i) alive, (ii) vulnerable, and (iii) dead states of the cell, and it was coupled with a tumor growth model. Our proposed methodology and preliminary results could be considered as a proof-of-principle for the significance of simulating accurately the hyperthermia-based tumor control involving the immune system. We also propose a method for the optimization of treatment by overcoming thermoresistance by biological means and specifically through the targeting of the heat shock protein 90 (HSP90), which plays a critical role in the thermotolerance of cells and tissues.
Highlights
Great advances have been made in early diagnosis and treatment of cancer, it remains one of the leading causes of death worldwide
Radiotherapy, chemotherapy, and surgery represent the main modalities of cancer treatment, while recent advances in the biology of cancer led to the development of new therapeutic strategies that result in the attack of the cancer cells by the immune system
Even though hyperthermia is not the preferred method of primary cancer treatment, historical evidence suggests that thermal therapy was used in ancient times; as Hippocrates stated “what medicines do not heal, the lance will; what the lance does not heal, fire will” [3]
Summary
Great advances have been made in early diagnosis and treatment of cancer, it remains one of the leading causes of death worldwide. Radiotherapy, chemotherapy, and surgery represent the main modalities of cancer treatment, while recent advances in the biology of cancer led to the development of new therapeutic strategies that result in the attack of the cancer cells by the immune system. Metallic nanoparticles (NPs), like gold NPs, strongly absorb and scatter light close to their localized surface plasmon resonance (LSPR) and can be used as heat emitters. As a result, they convert electromagnetic energy into heat, thereby causing hyperthermic cellular damage [5]. Heat delivered within the hyperthermia range (42–48 ◦C) induces tumor cell death, primarily by denaturation of essential cellular proteins [6]
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