Related Experiment Video
Updated: Jun 20, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Boosting Cancer Immunotherapy via Reversing PD-L1-Mediated Immunosuppression with a Molecularly Imprinted Lysosomal
Haifeng Lu1, Peixin Guan1, Shuxin Xu1
1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China.
Abstract:
Immune checkpoint blockade therapy has achieved important clinical advances in several types of tumors, particularly via targeting the PD-1/PD-L1 axis. However, existing therapeutic strategies that suppress the PD-1/PD-L1 signal pathway usually experience low treatment efficacy and the risk of causing autoimmune diseases. Herein, we report a cancer cell-targeted molecularly imprinted lysosomal nanodegrader (MILND) for boosting immune checkpoint blockade therapy against tumors. The MILND, imprinted with the N-terminal epitope of PD-L1 as an imprinting template, could specifically target the PD-L1 on tumor cells to promote cellular uptake. This process further induces the transport of PD-L1 into lysosomes for degradation, ultimately resulting in the downregulation of PD-L1 expression levels on tumor cells. As a result, a T cell-mediated immune response in the body was activated via the blockade of the PD-1/PD-L1 signaling pathway, which triggered a durable antitumor efficacy. In vivo experiments demonstrated that the MILND could effectively accumulate in tumor sites and exhibit strong tumor growth suppression efficacy in a xenograft tumor model without obvious side effects. Therefore, the MILND provides not only a promising strategy for boosting cancer immunotherapy but also insights for developing molecular imprinting-empowered nanomedicines.
Insights
A novel nanodegrader targets cancer cells to degrade PD-L1, enhancing immune checkpoint blockade therapy. This approach boosts T cell responses and antitumor efficacy with minimal side effects.
Area of Science:
- Biomedical Engineering
- Immunology
- Nanotechnology
Background:
- Immune checkpoint blockade therapy, particularly targeting the PD-1/PD-L1 axis, has shown clinical success in treating various tumors.
- Current strategies to inhibit the PD-1/PD-L1 pathway often suffer from low efficacy and potential autoimmune side effects.
Purpose of the Study:
- To develop a cancer cell-targeted molecularly imprinted lysosomal nanodegrader (MILND) to enhance immune checkpoint blockade therapy.
- To investigate the efficacy of MILND in downregulating PD-L1 expression and activating T cell-mediated antitumor immune responses.
Main Methods:
- Designed MILND imprinted with the N-terminal epitope of PD-L1 for specific tumor cell targeting.
- Investigated MILND-induced cellular uptake, lysosomal transport, and subsequent PD-L1 degradation.
- Evaluated the activation of T cell-mediated immunity and antitumor effects in a xenograft tumor model.
Main Results:
- MILND specifically targeted PD-L1 on tumor cells, promoting uptake and lysosomal degradation.
- Successful downregulation of PD-L1 expression on tumor cells was achieved.
- Activated T cell-mediated immune responses and demonstrated significant tumor growth suppression in vivo.
- MILND exhibited no obvious side effects in the xenograft model.
Conclusions:
- MILND offers a promising strategy for boosting cancer immunotherapy by enhancing immune checkpoint blockade.
- This approach provides a novel method for PD-L1 downregulation and T cell activation.
- Highlights the potential of molecular imprinting in developing advanced nanomedicines for cancer treatment.
More Related Videos
10:18Author Spotlight: Magnetic Fluorescent Bead-Based Dual-Reporter Flow Analysis of PDL1-Vaxx Peptide Vaccine-Induced Antibody Blockade of the PD-1/PD-L1 Interaction
Published on: July 7, 2023
07:04Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
