Self-reinforced photodynamic immunostimulator to downregulate and block PD-L1 for metastatic breast cancer treatment

Tumor cells overexpress programmed cell death ligand 1 (PD-L1) to impede immune responses and escape immune elimination. Development of effective combination regimens to sensitize immunotherapy is promising but always challenging. Herein, a self-reinforced photodynamic immunostimulator (designated a...

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Bibliographic Details
Published in:Biomaterials 2023-12, Vol.303, p.122392-122392, Article 122392
Main Authors: Qiu, Ziwen, Lu, Zhenming, Huang, Jiaqi, Zhong, Yingtao, Yan, Ni, Kong, Renjiang, Cheng, Hong
Format: Article
Language:English
Subjects:
B7-H1 Antigen - metabolism
biocompatible materials
breast neoplasms
Breast Neoplasms - drug therapy
cancer therapy
Cell Line, Tumor
Female
Humans
immunity
immunostimulants
Immunotherapy
ligands
metastasis
oxidative stress
peptides
phosphorylation
Photochemotherapy
photosensitizing agents
Photosensitizing Agents - therapeutic use
programmed cell death
protoporphyrin
signal transduction
transactivators
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Summary:Tumor cells overexpress programmed cell death ligand 1 (PD-L1) to impede immune responses and escape immune elimination. Development of effective combination regimens to sensitize immunotherapy is promising but always challenging. Herein, a self-reinforced photodynamic immunostimulator (designated as PCS) is constructed for metastatic breast cancer treatment through simultaneous downregulation and blockade of PD-L1. Specifically, PCS is prepared by encapsulating signal transducer and activator of transcription 3 (STAT3) inhibitor (Stattic) into photosensitizer (protoporphyrin IX) modified PD-L1 blockade peptide (CVRARTR) through drug self-assembly. PCS can facilitate the targeted drug accumulation in PD-L1 overexpressed breast cancer cells to block PD-L1 and inhibit the phosphorylation of STAT3 to downregulate PD-L1. Moreover, PCS increases intracellular oxidative stress to show a robust anti-proliferation effect through photodynamic therapy (PDT), which also triggers an immunogenic cell death (ICD) to expose the immunostimulatory signals. Consequently, the efficient PD-L1 inhibition and robust PDT of PCS synergistically suppress the malignant growth of breast cancer, and concurrently activate the systemic anti-tumor immunity for metastatic inhibition with no obvious side effects. Such a photodynamic immunostimulator may provide an effective combination regimen for therapies activated immunotherapy against metastatic breast cancer.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2023.122392