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Lactate oxidase/catalase-displaying nanoparticles efficiently consume lactate in the tumor microenvironment to effectively suppress tumor growth.
Choi, Hyukjun; Yeo, Mirae; Kang, Yujin; Kim, Hyo Jeong; Park, Seong Guk; Jang, Eunjung; Park, Sung Ho; Kim, Eunhee; Kang, Sebyung.
Afiliación
  • Choi H; Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea.
  • Yeo M; Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea.
  • Kang Y; Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea.
  • Kim HJ; Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea.
  • Park SG; Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea.
  • Jang E; Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea.
  • Park SH; Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea. parksu@unist.ac.kr.
  • Kim E; Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea. ehkim@unist.ac.kr.
  • Kang S; Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, South Korea. sabsab7@unist.ac.kr.
J Nanobiotechnology ; 21(1): 5, 2023 Jan 03.
Article en En | MEDLINE | ID: mdl-36597089
The aggressive proliferation of tumor cells often requires increased glucose uptake and excessive anaerobic glycolysis, leading to the massive production and secretion of lactate to form a unique tumor microenvironment (TME). Therefore, regulating appropriate lactate levels in the TME would be a promising approach to control tumor cell proliferation and immune suppression. To effectively consume lactate in the TME, lactate oxidase (LOX) and catalase (CAT) were displayed onto Aquifex aeolicus lumazine synthase protein nanoparticles (AaLS) to form either AaLS/LOX or AaLS/LOX/CAT. These complexes successfully consumed lactate produced by CT26 murine colon carcinoma cells under both normoxic and hypoxic conditions. Specifically, AaLS/LOX generated a large amount of H2O2 with complete lactate consumption to induce drastic necrotic cell death regardless of culture condition. However, AaLS/LOX/CAT generated residual H2O2, leading to necrotic cell death only under hypoxic condition similar to the TME. While the local administration of AaLS/LOX to the tumor site resulted in mice death, that of AaLS/LOX/CAT significantly suppressed tumor growth without any severe side effects. AaLS/LOX/CAT effectively consumed lactate to produce adequate amounts of H2O2 which sufficiently suppress tumor growth and adequately modulate the TME, transforming environments that are favorable to tumor suppressive neutrophils but adverse to tumor-supportive tumor-associated macrophages. Collectively, these findings showed that the modular functionalization of protein nanoparticles with multiple metabolic enzymes may offer the opportunity to develop new enzyme complex-based therapeutic tools that can modulate the TME by controlling cancer metabolism.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Neoplasias Límite: Animals Idioma: En Revista: J Nanobiotechnology Año: 2023 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Nanopartículas / Neoplasias Límite: Animals Idioma: En Revista: J Nanobiotechnology Año: 2023 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Reino Unido