Catalase-Gold Nanoaggregates Manipulate the Tumor Microenvironment and Enhance the Effect of Low-Dose Radiation Therapy by Reducing Hypoxia

Catalase-Gold Nanoaggregates Manipulate the Tumor Microenvironment and Enhance the Effect of Low-Dose Radiation Therapy by Reducing Hypoxia Publisher Pubmed

Najafi A^{1, 2} ; Keykhaee M³ ; Kazemi MH^{1, 2} ; Karimi MY⁴ ; Khorramdelazad H^{1, 5} ; Aghamohamadi N^{1, 2} ; Bolouri MR^{1, 2} ; Ghaffarinazari H⁶ ; Mirsharif ES⁷ ; Karimi M^{1, 2} ; Dehghan Manshadi HR⁸ ; Mahdavi SR⁹ ; Safari E^{1, 2} ; Jalali SA¹⁰ Show All Authors

Najafi A^{1, 2}
Keykhaee M³
Kazemi MH^{1, 2}
Karimi MY⁴
Khorramdelazad H^{1, 5}
Aghamohamadi N^{1, 2}
Bolouri MR^{1, 2}
Ghaffarinazari H⁶
Mirsharif ES⁷
Karimi M^{1, 2}
Dehghan Manshadi HR⁸
Mahdavi SR⁹
Safari E^{1, 2}
Jalali SA¹⁰
Falak R^{1, 2}
Khoobi M^{11, 12}

Show Affiliations

1. Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
2. Department of Immunology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
3. Department of Pharmaceutical Biomaterials and Medical Biomaterial Research Center (MBRC), Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
4. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran
5. Department of Immunology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
6. Department of Immunology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
7. Immunoregulation Research Center, Shahed University, Tehran, Iran
8. Department of Radiation Oncology, Hafte Tir Hospital, Iran University of Medical Sciences, Tehran, Iran
9. Radiation Biology Research Center& Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
10. Immunology Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
11. Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
12. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran

Source: Biomedicine and Pharmacotherapy Published:2023

Abstract

Radiotherapy as a standard method for cancer treatment faces tumor recurrence and antitumoral unresponsiveness. Suppressive tumor microenvironment (TME) and hypoxia are significant challenges affecting efficacy of radiotherapy. Herein, a versatile method is introduced for the preparation of pH-sensitive catalase-gold cross-linked nanoaggregate (Au@CAT) having acceptable stability and selective activity in tumor microenvironment. Combining Au@CAT with low-dose radiotherapy enhanced radiotherapy effects via polarizing protumoral immune cells to the antitumoral landscape. This therapeutic approach also attenuated hypoxia, confirmed by downregulating hypoxia hallmarks, such as hypoxia-inducible factor α-subunits (HIF-α), vascular endothelial growth factor (VEGF), and EGF. Catalase stability against protease digestion was improved significantly in Au@CAT compared to the free catalase. Moreover, minimal toxicity of Au@CAT on normal cells and increased reactive oxygen species (ROS) were confirmed in vitro compared with radiotherapy. Using the nanoaggregates combined with radiotherapy led to a significant reduction of immunosuppressive infiltrating cells such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (T-regs) compared to the other groups. While, this combined therapy could significantly increase the frequency of CD8+ cells as well as M1 to M2 macrophages (MQs) ratio. The combination therapy also reduced the tumor size and increased survival rate in mice models of colorectal cancer (CRC). Our results indicate that this innovative nanocomposite could be an excellent system for catalase delivery, manipulating the TME and providing a potential therapeutic strategy for treating CRC. © 2023

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Style	Citing Format
MLA	Najafi A, et al.. "Catalase-Gold Nanoaggregates Manipulate the Tumor Microenvironment and Enhance the Effect of Low-Dose Radiation Therapy by Reducing Hypoxia." Biomedicine and Pharmacotherapy, vol. 167, no. , 2023, pp. -.
APA	Najafi A, Keykhaee M, Kazemi MH, Karimi MY, Khorramdelazad H, Aghamohamadi N, Bolouri MR, Ghaffarinazari H, Mirsharif ES, Karimi M, Dehghan Manshadi HR, Mahdavi SR, Safari E, Jalali SA, Falak R, Khoobi M (2023). Catalase-Gold Nanoaggregates Manipulate the Tumor Microenvironment and Enhance the Effect of Low-Dose Radiation Therapy by Reducing Hypoxia. Biomedicine and Pharmacotherapy, 167(), -.
Chicago	Najafi A, Keykhaee M, Kazemi MH, Karimi MY, Khorramdelazad H, Aghamohamadi N, Bolouri MR, et al.. "Catalase-Gold Nanoaggregates Manipulate the Tumor Microenvironment and Enhance the Effect of Low-Dose Radiation Therapy by Reducing Hypoxia." Biomedicine and Pharmacotherapy 167, no. (2023): -.
Harvard	Najafi A et al. (2023) 'Catalase-Gold Nanoaggregates Manipulate the Tumor Microenvironment and Enhance the Effect of Low-Dose Radiation Therapy by Reducing Hypoxia', Biomedicine and Pharmacotherapy, 167(), pp. -.
Vancouver	Najafi A, Keykhaee M, Kazemi MH, Karimi MY, Khorramdelazad H, Aghamohamadi N, et al.. Catalase-Gold Nanoaggregates Manipulate the Tumor Microenvironment and Enhance the Effect of Low-Dose Radiation Therapy by Reducing Hypoxia. Biomedicine and Pharmacotherapy. 2023;167():-.
BibTex	@article{ author = {Najafi A and Keykhaee M and Kazemi MH and Karimi MY and Khorramdelazad H and Aghamohamadi N and Bolouri MR and Ghaffarinazari H and Mirsharif ES and Karimi M and Dehghan Manshadi HR and Mahdavi SR and Safari E and Jalali SA and Falak R and Khoobi M}, title = {Catalase-Gold Nanoaggregates Manipulate the Tumor Microenvironment and Enhance the Effect of Low-Dose Radiation Therapy by Reducing Hypoxia}, journal = {Biomedicine and Pharmacotherapy}, volume = {167}, number = {}, pages = {-}, year = {2023} }
RIS	TY - JOUR AU - Najafi A AU - Keykhaee M AU - Kazemi MH AU - Karimi MY AU - Khorramdelazad H AU - Aghamohamadi N AU - Bolouri MR AU - Ghaffarinazari H AU - Mirsharif ES AU - Karimi M AU - Dehghan Manshadi HR AU - Mahdavi SR AU - Safari E AU - Jalali SA AU - Falak R AU - Khoobi M TI - Catalase-Gold Nanoaggregates Manipulate the Tumor Microenvironment and Enhance the Effect of Low-Dose Radiation Therapy by Reducing Hypoxia JO - Biomedicine and Pharmacotherapy VL - 167 IS - SP - EP - PY - 2023 ER -

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