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Gemcitabine-loaded synthetic high-density lipoprotein preferentially eradicates hepatic monocyte-derived macrophages in mouse liver with colorectal cancer metastases.
Xiong, Feng-Qin; Zhang, Wen; Zheng, Chao; Li, Yu; Gong, Xiang; Zhang, Yuan; Wang, Hao; Zhang, Peng-Cheng; Li, Ya-Ping.
Afiliación
  • Xiong FQ; China State Institute of Pharmaceutical Industry, Shanghai, 201203, China.
  • Zhang W; State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Zheng C; China State Institute of Pharmaceutical Industry, Shanghai, 201203, China.
  • Li Y; State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Gong X; China State Institute of Pharmaceutical Industry, Shanghai, 201203, China.
  • Zhang Y; State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • Wang H; School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
  • Zhang PC; China State Institute of Pharmaceutical Industry, Shanghai, 201203, China.
  • Li YP; State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Acta Pharmacol Sin ; 44(11): 2331-2341, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37225846
Liver metastasis of colorectal cancer (CRC) is the critical cause of CRC-related death due to its unique immunosuppressive microenvironment. In this study we generated a gemcitabine-loaded synthetic high-density lipoprotein (G-sHDL) to reverse immunosuppression in livers with CRC metastases. After intravenous injection, sHDL targeted hepatic monocyte-derived alternatively activated macrophages (Mono-M2) in the livers of mice bearing both subcutaneous tumors and liver metastases. The G-sHDL preferentially eradicated Mono-M2 in the livers with CRC metastases, which consequently prevented Mono-M2-mediated killing of tumor antigen-specific CD8+ T cells in the livers and thus improved the densities of tumor antigen-specific CD8+ T cells in the blood, tumor-draining lymph nodes and subcutaneous tumors of the treated mice. While reversing the immunosuppressive microenvironment, G-sHDL also induced immunogenic cell death of cancer cells, promoted maturation of dendritic cells, and increased tumor infiltration and activity of CD8+ T cells. Collectively, G-sHDL inhibited the growth of both subcutaneous tumors and liver metastases, and prolonged the survival of animals, which could be further improved when used in conjunction with anti-PD-L1 antibody. This platform can be a generalizable platform to modulate immune microenvironment of diseased livers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Neoplasias Hepáticas Límite: Animals Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Colorrectales / Neoplasias Hepáticas Límite: Animals Idioma: En Revista: Acta Pharmacol Sin Asunto de la revista: FARMACOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos