ROS-Inducing Micelles Sensitize Tumor-Associated Macrophages to TLR3 Stimulation for Potent Immunotherapy

Liu, Lanlan1,2; He, Huamei1; Liang, Ruijing1; Yi, Huqiang1,3; Meng, Xiaoqing1,2; Chen, Zhikuan1,2; Pan, Hong1,2; Ma, Yifan1,4; Cai, Lintao1

2018-06

10.1021/acs.biomac.8b00239

BIOMACROMOLECULES   影响因子和分区

1525-7797

1526-4602

One approach to cancer immunotherapy is the repolarization of immunosuppressive tumor-associated macrophages (TAMs) to antitumor M1 macrophages. The present study developed galactose-functionalized zinc protoporphyrin IX (ZnPP) grafted poly(L-lysine)-b-poly(ethyleneglycol) polypeptide micelles (ZnPP PM) for TAM-targeted immunopotentiator delivery, which aimed at in vivo repolarization of TAMs to antitumor M1 macrophages. The outcomes revealed that ROS-inducing ZnPP PM demonstrated specificity for the in vitro and in vivo targeting of macrophages, elevated the level of ROS, and lowered STAT3 expression in BM-TAMs. Poly I:C (PIC, a TLR3 agonist)-loaded ZnPP PM (ZnPP PM/PIC) efficiently repolarized TAMs to M1 macrophages, which were reliant on ROS generation. Further, ZnPP PM/PIC substantially elevated the activated NK cells and T lymphocytes in B16-F10 melanoma tumors, which caused vigorous tumor regression. Therefore, the TAM-targeted transport of an immunologic adjuvant with ZnPP-grafted nanovectors may be a potential strategy to repolarize TAMs to Ml macrophages in situ for effective cancer immunotherapy.

SCI ; EI

英语

其他

SIAT Innovation Program for Excellent Young Researchers[Y7G005]

Biochemistry & Molecular Biology ; Chemistry ; Polymer Science

Biochemistry & Molecular Biology ; Chemistry, Organic ; Polymer Science

WOS:000435226200038

AMER CHEMICAL SOC

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Chinese Acad Sci, Shenzhen Inst Adv Technol, Guangdong Key Lab Nanomed, CAS Key Lab Hlth Informat,Inst Biomed & Biotechno, Shenzhen 518055, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Southern Univ Sci & Technol, Dept Mat Sci & Engn, Shenzhen 518055, Peoples R China
4.HRYZ Biotech Co, Shanghai 200122, Peoples R China

Liu, Lanlan,He, Huamei,Liang, Ruijing,et al. ROS-Inducing Micelles Sensitize Tumor-Associated Macrophages to TLR3 Stimulation for Potent Immunotherapy[J]. BIOMACROMOLECULES,2018,19(6):2146-2155.

Liu, Lanlan.,He, Huamei.,Liang, Ruijing.,Yi, Huqiang.,Meng, Xiaoqing.,...&Cai, Lintao.(2018).ROS-Inducing Micelles Sensitize Tumor-Associated Macrophages to TLR3 Stimulation for Potent Immunotherapy.BIOMACROMOLECULES,19(6),2146-2155.

Liu, Lanlan,et al."ROS-Inducing Micelles Sensitize Tumor-Associated Macrophages to TLR3 Stimulation for Potent Immunotherapy".BIOMACROMOLECULES 19.6(2018):2146-2155.