Self-Assembled PD-L1 Downregulator to Boost Photodynamic Activated Tumor Immunotherapy Through CDK5 Inhibition

被引：1

作者：

Yu, Bai-Xue ^{[1
,2
]}

Liu, Yi-Bin ^{[1
,2
]}

Chen, Xia-Yun ^{[1
,2
]}

Zhang, Wei ^{[1
,2
]}

Cen, Yi ^{[1
,2
]}

Yan, Meng-Yi ^{[1
,2
]}

Liu, Qian-Qian ^{[1
,2
]}

Li, Shi-Ying ^{[1
,2
]}

机构：

[1] Guangzhou Med Univ, Affiliated Hosp 5, Sch Pharmaceut Sci, Guangdong Prov Key Lab Mol Target & Clin Pharmacol, Guangzhou 511436, Peoples R China

[2] Guangzhou Med Univ, Sch Pharmaceut Sci, State Key Lab Resp Dis, Guangzhou 511436, Peoples R China

来源：

SMALL | 2024年 / 20卷 / 33期

基金：

中国国家自然科学基金;

关键词：

cyclin-dependent kinase 5 (CDK5); immunogenic cell death; immunotherapy; photodynamic therapy; programmed death receptor ligand 1 (PD-L1); IMMUNOGENIC CELL-DEATH; CANCER;

D O I：

10.1002/smll.202311507

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The immunosuppressive characteristics and acquired immune resistance can restrain the therapy-initiated anti-tumor immunity. In this work, an antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is fabricated to boost photodynamic activated immunotherapy through cyclin-dependent kinase 5 (CDK5) inhibition. Among which, FDA approved photosensitizer of chlorin e6 (Ce6) and preclinical available CDK5 inhibitor of seliciclib (Se) are utilized to prepare the nanomedicine of CeSe through self-assembly technique without drug excipient. Nanoscale CeSe exhibits an increased stability and drug delivery efficiency, contributing to intracellular production of reactive oxygen species (ROS) for robust photodynamic therapy (PDT). The PDT of CeSe can not only suppress the primary tumor growth, but also induce the immunogenic cell death (ICD) to release tumor associated antigens. More importantly, the CDK5 inhibition by CeSe can downregulate PD-L1 to re-activate the systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. This work provides an antibody free strategy to activate systemic immune response for metastatic tumor treatment, which may accelerate the development of translational nanomedicine with sophisticated mechanism. An antibody free programmed death receptor ligand 1 (PD-L1) downregulator (designated as CeSe) is developed based on chlorin e6 (Ce6) and seliciclib (Se), which can inhibit cyclin-dependent kinase 5 (CDK5) to downregulate PD-L1 for re-activation of systemic anti-tumor immunity by decreasing the tumor immune escape and therapy-induced acquired immune resistance. image

引用

页数：12