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Published on: February 3, 2023
Engineered Magnetic Resonance Nanoprobes for Visualizing Tumor Programmed Cell Death Ligand 1 Level and Enhancing
Xiao Sun1,2, Yufang Gong1, Haiyan Ge1
1Department of Pharmacy, Shandong Cancer Hospital and Institute, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250117, China.
Abstract:
Visualizing tumor programmed cell death ligand 1 (PD-L1) expression and synchronously using this target for effective tumor therapy present great prospects for clinical application. In this study, a gadolinium-hybridized platinum nanoplatform with dimeric PD-L1-antagonistic affibody (ZPD-L1) (GPPZ) was constructed. Leveraging the specific binding between ZPD-L1 and the tumor surface, ZPD-L1 could endow this nanoplatform with efficient PD-L1 targeting, enabling the efficient magnetic resonance imaging (MRI) visualization of PD-L1 expression. GPPZ, through its catalase- and peroxidase-like activities, can catalyze the production of O2 and the production of •OH, respectively, sensitizing radiotherapy and enhancing immunogenic cell death. In addition, ZPD-L1 can also terminate T cells' immune suppression by effectively inhibiting interactions of PD-1/PD-L1 to further enhance tumor immunotherapy. Systemic delivery of GPPZ resulted in MRI contrast enhancement of tumors with high levels of PD-L1 expression. Importantly, no obvious side effects can be observed in both histological and hematology examination. Therefore, this nanoplatform demonstrated promise for enhanced MRI visualization of tumor PD-L1 level and synergistic radio immunotherapy.
Insights
This study introduces a novel nanoplatform for visualizing tumor programmed cell death ligand 1 (PD-L1) expression using MRI. The platform enhances radiotherapy and immunotherapy by targeting PD-L1, offering a promising approach for cancer treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Tumor programmed cell death ligand 1 (PD-L1) expression is a key target for cancer therapy and imaging.
- Current methods for visualizing PD-L1 expression and therapeutic targeting are limited.
Purpose of the Study:
- To develop a novel nanoplatform for simultaneous visualization of PD-L1 expression and synergistic cancer therapy.
- To evaluate the efficacy of the nanoplatform in magnetic resonance imaging (MRI) and combined radio-immunotherapy.
Main Methods:
- Construction of a gadolinium-hybridized platinum nanoplatform functionalized with PD-L1-antagonistic affibody (ZPD-L1), termed GPPZ.
- Utilizing GPPZ for targeted MRI visualization of PD-L1 expression in tumors.
- Assessing GPPZ's catalytic activities for radiotherapy sensitization and immunogenic cell death induction.
- Evaluating GPPZ's role in enhancing tumor immunotherapy by inhibiting PD-1/PD-L1 interactions.
Main Results:
- GPPZ demonstrated efficient PD-L1 targeting and enabled MRI visualization of PD-L1 expression in tumors.
- The nanoplatform catalyzed oxygen and hydroxyl radical production, sensitizing radiotherapy and enhancing immunogenic cell death.
- GPPZ effectively inhibited T cell immune suppression, boosting immunotherapy.
- Systemic delivery of GPPZ showed no significant side effects in histological and hematological examinations.
Conclusions:
- The developed GPPZ nanoplatform shows significant promise for enhanced MRI visualization of tumor PD-L1 levels.
- GPPZ offers a synergistic approach for combined radio-immunotherapy, improving cancer treatment strategies.
