Precise HER2 Protein Degradation via Peptide‐Conjugated Photodynamic Therapy for Enhanced Breast Cancer Immunotherapy

Breast cancer, the most prevalent malignancy among women, frequently exhibits high HER2 expression, making HER2 a critical therapeutic target. Traditional treatments combining the anti‐HER2 antibody trastuzumab with immunotherapy face limitations due to toxicity and tumor microenvironment immunosupp...

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Bibliographic Details
Published in:Advanced science Vol. 12; no. 2; pp. e2410778 - n/a
Main Authors: Guo, Changyong, Gao, Fei, Wu, Guoyuan, Li, Jinqiu, Sheng, Chunquan, He, Shipeng, Hu, Honggang
Format: Journal Article
Language:English
Published: Germany John Wiley & Sons, Inc 01.01.2025
John Wiley and Sons Inc
Wiley
Subjects:
Animals
Antibodies
Antigens
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - immunology
Breast Neoplasms - metabolism
Breast Neoplasms - therapy
Cancer therapies
Cell Line, Tumor
Chlorophyll - analogs & derivatives
Chlorophyll - pharmacology
Cytotoxicity
Drug development
Drug resistance
Female
gelatinase responsive peptides
Humans
immune induction
Immunotherapy
Immunotherapy - methods
Lymphocytes
Mice
Mice, Inbred BALB C
Morphology
Nanomaterials
Nanoparticles
Nanoparticles - chemistry
Peptides
Phase transitions
Photochemotherapy - methods
Photodegradation
photodynamic immunotherapy
Photosensitizing Agents - pharmacology
photo‐controlled her2 protein degradation
Physiology
Proteins
Reactive Oxygen Species - metabolism
Receptor, ErbB-2 - metabolism
photo‐controlled her2 protein degradation
breast cancer
gelatinase responsive peptides
immune induction
photodynamic immunotherapy
ISSN:2198-3844, 2198-3844
Online Access:Get full text
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Summary:Breast cancer, the most prevalent malignancy among women, frequently exhibits high HER2 expression, making HER2 a critical therapeutic target. Traditional treatments combining the anti‐HER2 antibody trastuzumab with immunotherapy face limitations due to toxicity and tumor microenvironment immunosuppression. This study introduces an innovative strategy combining HER2‐targeting peptides with the photosensitizer (PSs) pyropheophorbide‐a (Pha) via a gelatinase‐cleavable linker, forming self‐assembling nanoparticles. These nanoparticles actively target breast cancer cells and generate reactive oxygen species (ROS) under near‐infrared light, effectively degrading HER2 proteins. Upon internalization, the linker is cleaved, releasing Pha‐PLG and enhancing intracellular photodynamic therapy (PDT). The Pha‐PLG molecules self‐assemble into nanofibers, prolonging circulation, boosting immune induction, and activating CD8+ T cells, thus promoting a robust anti‐tumor immune response. In vivo, studies confirm superior biosafety, tumor targeting, and HER2 degradation, with increased cytotoxic T cell activity and improved antitumor immunity. This integrated strategy offers a promising new avenue for breast cancer treatment. The self‐assembling nanomaterial PPC facilitates photo‐controlled degradation of the HER2 protein in conjunction with PDT, thereby reshaping the tumor microenvironment and augmenting the efficacy of tumor immunotherapy.
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ISSN:2198-3844
2198-3844
DOI:10.1002/advs.202410778