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ACS Nano, Jan 06 2025, | https://doi.org/10.1021/acsnano.4c16128 Cell-Penetrating Peptide Like Anti-Programmed Cell Death-Ligand 1 Peptide Conjugate-Based Self-Assembled Nanoparticles for Immunogenic Photodynamic Therapy

Jun-Hyuck Lee ¹, Seong-Bin Yang ¹, Seong Jin Park ², Seho Kweon ³, Gaeun Ma ¹, Minho Seo ¹, Ha Rin Kim ^4,5, Tae-Bong Kang ¹, Ji-Hong Lim¹, Jooho Park¹

¹BK21 Program, Department of Applied Life Science, Konkuk University, Chungju 27478, Republic of Korea.
²Department of Research, Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea.
³College of Pharmacy, Chonnam National University, Gwangju 61186, Republic of Korea.
⁴School of Medicine, Stanford University, Stanford, California 94305, United States.
⁵Department of Biopharmaceutical Chemistry, Kookmin University, Seoul 02707, Republic of Korea.

J.-H.L., S.-B.Y., S.-J.P. contributed equally.
Corresponding Authors : Ji-Hong Lim, Jooho Park

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.

논문정보

형식Research article
게재일2025년 01월 (BRIC 등록일 2025-01-07)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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