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Comprehensive evaluation of biopolymer immune implants for peritoneal metastasis carcinoma therapy.
Si, Xinghui; Ji, Guofeng; Ma, Sheng; Chen, Hongyu; Shi, Zhiyuan; Zhang, Yu; Tang, Zhaohui; Song, Wantong; Chen, Xuesi.
Affiliation
  • Si X; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China.
  • Ji G; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Xuanwu Hospital, Capital Medical University, Beijing 100010, PR China.
  • Ma S; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China.
  • Chen H; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China.
  • Shi Z; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China.
  • Zhang Y; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China.
  • Tang Z; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China.
  • Song W; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China. Electronic a
  • Chen X; Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, PR China; Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, PR China; University of Science and Technology of China, Hefei 230026, PR China. Electronic a
J Control Release ; 353: 289-302, 2023 01.
Article in En | MEDLINE | ID: mdl-36403683
ABSTRACT
Immunotherapy has been widely used in the treatment of advanced stage cancers with spreading metastases, while the fully activation of immune system often requires sustained and long-acting immune stimulation by immunotherapeutic agents. In previous studies, we designed a biopolymer immune implant by dynamic covalent bonds and achieved sustained release of loaded immunotherapeutic agents, thus stimulated systemic immune activation and elicited immune memory effects. Herein, we further optimized the implants and carried out a comprehensive evaluation of the implants on peritoneal metastasis carcinoma (PMC) therapy. Our results showed that the implants fabricated with 8-arm polyethylene glycol amine (8-arm PEG-NH2) and 40% oxidation degree dextran (ODEX) exhibited a satisfactory degradation time for activating the antitumor immunity. The drug combination of oxaliplatin (OxP) and resiquimod (R848) could be sustainably released from the implants for 18 days. The implants cured 75% of mice with PMC and elicited immune memory effects to resist tumor re-challenge without obvious side effects observed. Mechanism analysis revealed that the implants could serve as an in-situ vaccine to enhance the infiltration of activated dendritic cells (DCs), T cells and natural killer (NK) cells inside the tumor, as well as increase the serum tumor necrosis factor α (TNF-α), interferon-γ (IFN-γ) and interleukin 12 (IL-12) levels. These results strongly support the clinical translation potential of this sustained released biopolymer immune implants for PMC therapy.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peritoneal Neoplasms / Carcinoma Limits: Animals Language: En Journal: J Control Release Journal subject: FARMACOLOGIA Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Peritoneal Neoplasms / Carcinoma Limits: Animals Language: En Journal: J Control Release Journal subject: FARMACOLOGIA Year: 2023 Document type: Article