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Tumor Microenvironment-Responsive Nanocapsule Delivery CRISPR/Cas9 to Reprogram the Immunosuppressive Microenvironment in Hepatoma Carcinoma.
He, Lei; Li, Zhaozhao; Su, Danjie; Du, Haichen; Zhang, Kuo; Zhang, Wangqian; Wang, Shuning; Xie, Fei; Qiu, Yueyuan; Ma, Shuangxin; Shi, Gege; Yu, Duo; Lei, Xiaoying; Li, Weina; Li, Meng; Wang, Zhaowei; Gu, Jintao; Zhang, Yingqi.
Afiliación
  • He L; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Li Z; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Su D; Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
  • Du H; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Zhang K; Department of Oncology, 940th Hospital, Joint Logistic Support Force, Lanzhou, 730050, China.
  • Zhang W; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Wang S; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Xie F; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Qiu Y; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Ma S; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Shi G; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Yu D; College of Life Sciences, Northwest University, Xi'an, 710069, China.
  • Lei X; Department of Neurosurgery, General Hospital of Central Theater Command, Wuhan, 430012, China.
  • Li W; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Li M; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Wang Z; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Gu J; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
  • Zhang Y; State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Biopharmaceutics, School of Pharmacy, The Fourth Military Medical University, Xi'an, 710032, China.
Adv Sci (Weinh) ; 11(26): e2403858, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38704691
ABSTRACT
Cancer immunotherapy has demonstrated significant efficacy in various tumors, but its effectiveness in treating Hepatocellular Carcinoma (HCC) remains limited. Therefore, there is an urgent need to identify a new immunotherapy target and develop corresponding intervention strategies. Bioinformatics analysis has revealed that growth differentiation factor 15 (GDF15) is highly expressed in HCC and is closely related to poor prognosis of HCC patients. The previous study revealed that GDF15 can promote immunosuppression in the tumor microenvironment. Therefore, knocking out GDF15 through gene editing could potentially reverse the suppressive tumor immune microenvironment permanently. To deliver the CRISPR/Cas9 system specifically to HCC, nanocapsules (SNC) coated with HCC targeting peptides (SP94) on their surface is utilized. These nanocapsules incorporate disulfide bonds (SNCSS) that release their contents in the tumor microenvironment characterized by high levels of glutathione (GSH). In vivo, the SNCSS target HCC cells, exert a marked inhibitory effect on HCC progression, and promote HCC immunotherapy. Mechanistically, CyTOF analysis showed favorable changes in the immune microenvironment of HCC, immunocytes with killer function increased and immunocytes with inhibitive function decreased. These findings highlight the potential of the CRISPR-Cas9 gene editing system in modulating the immune microenvironment and improving the effectiveness of existing immunotherapy approaches for HCC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Nanocápsulas / Microambiente Tumoral / Sistemas CRISPR-Cas / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Nanocápsulas / Microambiente Tumoral / Sistemas CRISPR-Cas / Neoplasias Hepáticas Límite: Animals / Humans Idioma: En Revista: Adv Sci (Weinh) Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Alemania