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Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
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Cell-Penetrating Peptide Like Anti-Programmed Cell Death-Ligand 1 Peptide Conjugate-Based Self-Assembled
Jun-Hyuck Lee1, Seong-Bin Yang1, Seong Jin Park2
1BK21 Program, Department of Applied Life Science, Konkuk University, Chungju 27478, Republic of Korea.
Abstract:
The tumor-specific efficacy of the most current anticancer therapeutic agents, including antibody-drug conjugates (ADCs), oligonucleotides, and photosensitizers, is constrained by limitations such as poor cell penetration and low drug delivery. In this study, we addressed these challenges by developing, a positively charged, amphiphilic Chlorin e6 (Ce6)-conjugated, cell-penetrating anti-PD-L1 peptide nanomedicine (CPPD1) with enhanced cell and tissue permeability. The CPPD1 molecule, a bioconjugate of a hydrophobic photosensitizer and strongly positively charged programmed cell death-ligand 1 (PD-L1) binding cell-penetrating peptide (CPP), is capable of self-assembling into nanoparticles with an average size of 199 nm in aqueous solution without the need for any carriers. These carrier-free nanoparticles possess the ability to penetrate the cell membrane of cancer cells and target tumors expressing PD-L1 on their surface. Notably, CPPD1 nanoparticles effectively blocked programmed cell death-1 (PD-1)/PD-L1 interactions and reduced PD-L1 expression via lysosomal degradation. They also demonstrated the responsiveness of CPPD1 nanoparticles in photodynamic therapy (PDT) to a 635 nm laser, leading to the generation of ROS, and induction of various immunogenic cell deaths (ICD). Highly penetrating CPPD1 nanoparticles could immunogenically modulate the microenvironment of CT26 cancer and were also effective in treating abscopal metastatic tumors, addressing major limitations of traditional PDT.
Insights
This study introduces a novel nanomedicine (CPPD1) that enhances anticancer therapy by improving drug delivery and cell penetration. CPPD1 targets tumors, blocks PD-1/PD-L1 interactions, and shows promise in photodynamic therapy and treating metastatic tumors.
Area of Science:
- Nanomedicine
- Cancer Therapy
- Immunotherapy
Background:
- Current anticancer agents like antibody-drug conjugates face limitations in cell penetration and drug delivery.
- Poor drug delivery and cell penetration hinder the efficacy of many advanced cancer therapeutics.
- Targeting PD-L1 is a key strategy in cancer immunotherapy, but delivery challenges remain.
Purpose of the Study:
- To develop a novel, carrier-free nanomedicine for enhanced anticancer efficacy.
- To create a positively charged, amphiphilic Chlorin e6 (Ce6)-conjugated, cell-penetrating anti-PD-L1 peptide nanomedicine (CPPD1).
- To improve cell and tissue permeability for better drug delivery and tumor targeting.
Main Methods:
- CPPD1 self-assembles into nanoparticles (199 nm) from a bioconjugate of photosensitizer (Ce6) and a PD-L1 binding cell-penetrating peptide (CPP).
- Investigated nanoparticle penetration into cancer cells and targeting of PD-L1 expressing tumors.
- Evaluated the blockade of PD-1/PD-L1 interactions, PD-L1 expression reduction, and photodynamic therapy (PDT) response using a 635 nm laser.
Main Results:
- CPPD1 nanoparticles demonstrated enhanced cell and tissue permeability, effectively penetrating cancer cell membranes.
- CPPD1 nanoparticles successfully blocked PD-1/PD-L1 interactions and reduced PD-L1 expression via lysosomal degradation.
- Photodynamic therapy with CPPD1 nanoparticles induced reactive oxygen species (ROS) and immunogenic cell death (ICD), modulated the tumor microenvironment, and treated abscopal metastatic tumors.
Conclusions:
- CPPD1 represents a promising carrier-free nanomedicine overcoming limitations of traditional anticancer agents.
- The developed nanomedicine enhances drug delivery, targets tumors effectively, and shows potential in immunotherapy and PDT.
- CPPD1's ability to modulate the tumor microenvironment and treat metastatic tumors addresses key challenges in cancer therapy.
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