期刊
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
卷 177, 期 -, 页码 175-183出版社
ELSEVIER
DOI: 10.1016/j.ejpb.2022.07.002
关键词
Chemo-immunotherapy; Microenvironment-responsive; Macrophages; M1 phenotype; Drug carrier
资金
- General Program of China Post- doctoral Science Foundation [2022M711369]
- National Natural Science Foundation of China [82000808]
- Innovation and Application Project of Medical and Public Health Technology of Wuxi Science and Technology [N20202005]
- Major Special Fund for Translational Medicine [2020ZHZD03]
- Fundamental Research Funds for the Central Universities [JUSRP12048]
- Fund of Wuxi Healthcare Commission [M202004]
- Suzhou Sci- ence and Technology Council [SNG201907]
- Natural Science Research Project of Universities in Jiangsu Province [20KJB330002]
In this study, therapeutic nanoparticles were developed to deliver doxorubicin and IL-12 for chemo-immunotherapy combination therapy on liver cancer. The nanoparticles showed prolonged circulation in blood, efficient accumulation in tumors, and inhibition of tumor growth.
Chemo-immunotherapy has gained increasing attention as one of the most promising combination therapy strategies to battle cancer. In this study, the therapeutic nanoparticles (TNPs) co-delivering doxorubicin (DOX) and IL-12 (IL-12) were developed for chemo-immunotherapy combination therapy on liver cancer. TNPs were synthesized based on the ionic interactions between cationic chitosan (Ch) and anionic poly-(glutamic acid) (PGA). DOX and IL-12 loaded in TNPs presented prolonged circulation in blood, efficient accumulation in tu-mors, and internalization in tumor cells. After that, DOX and IL-12 were co-released in the tumor microenvi-ronment. The locally responsive property of TNPs could subsequently re-educate macrophages. More significantly, TNPs with no obvious side effects can remarkably inhibit the H22 tumor growth in vivo. A low dosage of loaded IL-12 in TNPs can effectively polarize macrophages toward the M1 phenotype to reduce tumor burden, further enhancing the antitumor efficacy. Our results suggest that the self-stabilized TNPs could be a secure and effective drug carrier for intravenous administration when deprived of protective agents.
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