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Tumor microenvironment responsive liposomes blocking CXCL12/CXCR4 pathway and synergistically enhancing immune efficacy of anti-PD-L1
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Ru-dong WANG1, 2, Yi-wei PENG1, 2, Zhen-zhen YANG1, 2, Yi-tian DU1, 2, Meng LIN1, 2, Qi SUN1, 2, Xian-rong QI1, 2, *
Acta Pharmaceutica Sinica | 2022, 57(1) : 178 - 187
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Acta Pharmaceutica Sinica | 2022, 57(1): 178-187
• Original Articles •
Tumor microenvironment responsive liposomes blocking CXCL12/CXCR4 pathway and synergistically enhancing immune efficacy of anti-PD-L1
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Ru-dong WANG1, 2, Yi-wei PENG1, 2, Zhen-zhen YANG1, 2, Yi-tian DU1, 2, Meng LIN1, 2, Qi SUN1, 2, Xian-rong QI1, 2, *
Affiliations
  • 1. School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
  • 2. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Beijing 100191, China
Published: 2022-01-12 doi: 10.16438/j.0513-4870.2021-0967
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Blocking immune checkpoint programmed cell death receptor 1 (PD-1) or programmed death receptor-ligand 1 (PD-L1) can enhance anti-tumor activity of effector T cells. However, the lack of response in many patients to PD-1/PD-L1 therapy remains a question. Improving the immunosuppressive tumor microenvironment (TME) to enhance the efficacy of immune checkpoint inhibitors has become a promising cancer treatment strategy. We constructed a liposome system (PD-L1/siCXCL12-Lp) of CXCL12 siRNA and anti-PD-L1 peptide with matrix metalloproteinases (MMPs) responsiveness, which combined the TME regulation of siCXCL12 and the immune regulation of anti-PD-L1 peptide. All animal experiments were approved by the Biomedical Ethics Committee of Peking University. The authors found that PD-L1/siCXCL12-Lp directly down-regulated the expression of CXCL12 in vitro (33.8%) and in vivo (15.5%). It also effectively increased the ratio of CD8+/Treg by 20.0%, which helped the anti-PD-L1 peptide to better exert its immune effect. The combination therapy significantly inhibited tumor growth (52.08%) with great safety, which explored a new idea for cancer immunotherapy.

liposome  /  small interfering ribonucleic acid  /  C-X-C chemokine ligand 12/C-X-C chemokine receptor type 4  /  programmed cell death protein 1/programmed death receptor-ligand 1  /  matrix metalloproteinase-2
Ru-dong WANG, Yi-wei PENG, Zhen-zhen YANG, Yi-tian DU, Meng LIN, Qi SUN, Xian-rong QI. Tumor microenvironment responsive liposomes blocking CXCL12/CXCR4 pathway and synergistically enhancing immune efficacy of anti-PD-L1[J]. Acta Pharmaceutica Sinica, 2022 , 57 (1) : 178 -187 . DOI: 10.16438/j.0513-4870.2021-0967
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Article Info
doi: 10.16438/j.0513-4870.2021-0967
  • Receive Date：2021-06-30
  • Online Date：2025-12-22
  • Published：2022-01-12
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History
  • Received：2021-06-30
  • Revised：2021-07-22
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Affiliations
    1. School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
    2. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery System, Beijing 100191, China
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表12种不同金属材料的力学参数
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Family		 属数
Number of
genus		 种数
Number of
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鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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