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Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines.
Yang, Kai; Bai, Bing; Lei, Jiaqi; Yu, Xinyang; Qi, Shaolong; Wang, Yangfan; Huang, Feihe; Tong, Zaizai; Yu, Guocan.
Afiliação
  • Yang K; Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, People's Republic of China.
  • Bai B; Stoddart Institute of Molecular Science, Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
  • Lei J; Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, People's Republic of China.
  • Yu X; Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, People's Republic of China.
  • Qi S; Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, People's Republic of China.
  • Wang Y; Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, People's Republic of China.
  • Huang F; Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Department of Chemistry, Tsinghua University, Beijing 100084, People's Republic of China.
  • Tong Z; Stoddart Institute of Molecular Science, Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
  • Yu G; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311215, People's Republic of China.
J Am Chem Soc ; 146(17): 11679-11693, 2024 May 01.
Article em En | MEDLINE | ID: mdl-38482849
ABSTRACT
Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Vacinas Anticâncer / Nanopartículas / Lipídeos / Lipossomos Limite: Animals / Humans Idioma: En Revista: J Am Chem Soc Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Mensageiro / Vacinas Anticâncer / Nanopartículas / Lipídeos / Lipossomos Limite: Animals / Humans Idioma: En Revista: J Am Chem Soc Ano de publicação: 2024 Tipo de documento: Article