Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling

Fang-Chu Lin, Chao-Hsiung Hsu, Yung-Ya Lin Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA Background: Nano-therapeutic utilizing hyperthermia therapy in combination with chemotherapy, surgery, and radiation is known to treat various types of cancer. These...

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Autores principales:	Lin FC, Hsu CH, Lin YY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	nano-therapeutic nanomedicine hyperthermia heat shock protein cancer immunotherapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c96039b2b8f64ca1bcb98f4eb111e998
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spelling	oai:doaj.org-article:c96039b2b8f64ca1bcb98f4eb111e9982021-12-02T02:18:14ZNano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling1178-2013https://doaj.org/article/c96039b2b8f64ca1bcb98f4eb111e9982018-06-01T00:00:00Zhttps://www.dovepress.com/nano-therapeutic-cancer-immunotherapy-using-hyperthermia-induced-heat--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Fang-Chu Lin, Chao-Hsiung Hsu, Yung-Ya Lin Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA Background: Nano-therapeutic utilizing hyperthermia therapy in combination with chemotherapy, surgery, and radiation is known to treat various types of cancer. These cancer treatments normally focus on reducing tumor burden. Nevertheless, it is still challenging to confine adequate thermal energy in a tumor and obtain a complete tumor ablation to avoid recurrence and metastasis while leaving normal tissues unaffected. Consequently, it is critical to attain an alternative tumor-killing mechanism to circumvent these challenges. Studies have demonstrated that extracellular heat shock proteins (HSPs) activate antitumor immunity during tumor cell necrosis. Such induced immunity was further shown to assist in regressing tumor and reducing recurrence and metastasis. However, only a narrow range of thermal dose is reported to be able to acquire the optimal antitumor immune outcome. Consequently, it is crucial to understand how extracellular HSPs are generated.Materials and methods: In this work, a predictive model integrating HSP synthesis mechanism and cell death model is proposed to elucidate the HSP involvement in hyperthermia cancer immune therapy and its relation with dead tumor cells. This new model aims to provide insights into the thermally released extracellular HSPs by dead tumor cells for a more extensive set of conditions, including various temperatures and heating duration time.Results: Our model is capable of predicting the optimal thermal parameters to generate maximum HSPs for stimulating antitumor immunity, promoting tumor regression, and reducing metastasis. The obtained nonlinear relation between extracellular HSP concentration and increased dead cell number, along with rising temperature, shows that only a narrow range of thermal dose is able to generate the optimal antitumor immune result.Conclusion: Our predictive model is capable of predicting the optimal temperature and exposure time to generate HSPs involved in the antitumor immune activation, with a goal to promote tumor regression and reduce metastasis. Keywords: nano-therapeutic, nanomedicine, hyperthermia, heat shock protein, cancer immunotherapyLin FCHsu CHLin YYDove Medical Pressarticlenano-therapeuticnanomedicinehyperthermiaheat shock proteincancer immunotherapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 3529-3539 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	nano-therapeutic nanomedicine hyperthermia heat shock protein cancer immunotherapy Medicine (General) R5-920
spellingShingle	nano-therapeutic nanomedicine hyperthermia heat shock protein cancer immunotherapy Medicine (General) R5-920 Lin FC Hsu CH Lin YY Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling
description	Fang-Chu Lin, Chao-Hsiung Hsu, Yung-Ya Lin Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, USA Background: Nano-therapeutic utilizing hyperthermia therapy in combination with chemotherapy, surgery, and radiation is known to treat various types of cancer. These cancer treatments normally focus on reducing tumor burden. Nevertheless, it is still challenging to confine adequate thermal energy in a tumor and obtain a complete tumor ablation to avoid recurrence and metastasis while leaving normal tissues unaffected. Consequently, it is critical to attain an alternative tumor-killing mechanism to circumvent these challenges. Studies have demonstrated that extracellular heat shock proteins (HSPs) activate antitumor immunity during tumor cell necrosis. Such induced immunity was further shown to assist in regressing tumor and reducing recurrence and metastasis. However, only a narrow range of thermal dose is reported to be able to acquire the optimal antitumor immune outcome. Consequently, it is crucial to understand how extracellular HSPs are generated.Materials and methods: In this work, a predictive model integrating HSP synthesis mechanism and cell death model is proposed to elucidate the HSP involvement in hyperthermia cancer immune therapy and its relation with dead tumor cells. This new model aims to provide insights into the thermally released extracellular HSPs by dead tumor cells for a more extensive set of conditions, including various temperatures and heating duration time.Results: Our model is capable of predicting the optimal thermal parameters to generate maximum HSPs for stimulating antitumor immunity, promoting tumor regression, and reducing metastasis. The obtained nonlinear relation between extracellular HSP concentration and increased dead cell number, along with rising temperature, shows that only a narrow range of thermal dose is able to generate the optimal antitumor immune result.Conclusion: Our predictive model is capable of predicting the optimal temperature and exposure time to generate HSPs involved in the antitumor immune activation, with a goal to promote tumor regression and reduce metastasis. Keywords: nano-therapeutic, nanomedicine, hyperthermia, heat shock protein, cancer immunotherapy
format	article
author	Lin FC Hsu CH Lin YY
author_facet	Lin FC Hsu CH Lin YY
author_sort	Lin FC
title	Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling
title_short	Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling
title_full	Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling
title_fullStr	Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling
title_full_unstemmed	Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling
title_sort	nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/c96039b2b8f64ca1bcb98f4eb111e998
work_keys_str_mv	AT linfc nanotherapeuticcancerimmunotherapyusinghyperthermiainducedheatshockproteinsinsightsfrommathematicalmodeling AT hsuch nanotherapeuticcancerimmunotherapyusinghyperthermiainducedheatshockproteinsinsightsfrommathematicalmodeling AT linyy nanotherapeuticcancerimmunotherapyusinghyperthermiainducedheatshockproteinsinsightsfrommathematicalmodeling
_version_	1718402555731509248

Nano-therapeutic cancer immunotherapy using hyperthermia-induced heat shock proteins: insights from mathematical modeling

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