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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Vydáno v:	Advanced science Ročník 12; číslo 2; s. e2410778 - n/a
Hlavní autoři:	Guo, Changyong, Gao, Fei, Wu, Guoyuan, Li, Jinqiu, Sheng, Chunquan, He, Shipeng, Hu, Honggang
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Germany John Wiley & Sons, Inc 01.01.2025 John Wiley and Sons Inc Wiley
Témata:	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
On-line přístup:	Získat plný text
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2198-3844 2198-3844
DOI:	10.1002/advs.202410778