Bi-Functional Topospecific Nanoparticles to Promote Immune-Tumor Cell Engagement as A New Immunotherapeutic Strategy

© 2025 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - (2025) vom: 24. Sept., Seite e18838
1. Verfasser: Ortuño-Bernal, Alba (VerfasserIn)
Weitere Verfasser: Clara-Trujillo, Sandra, Lucena-Sánchez, Elena, Hicke, Francisco J, Escudero, Andrea, Pradana-López, Sandra, Jiménez-Alduan, Nelia, Díez, Paula, García-Fernández, Alba, Martínez-Máñez, Ramón
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2025
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article PD‐1 communication immunotherapy nanoparticles pHLIP
Beschreibung
Zusammenfassung:© 2025 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.
Cancer immunotherapy has emerged as a promising alternative approach, enabling the body's immune system to fight cancer. Cytotoxic T cells play a pivotal role in recognizing and eliminating tumor cells, and their effectiveness relies on establishing a physical interaction and efficient communication with cancer cells. However, this communication is often disrupted by immune escape mechanisms, allowing cancer progression. A versatile nanoplatform is developed to restore cellular connection using Janus mesoporous silica-Au nanoparticle (J-pHLIP-PD1), including specific binding sites on opposite faces for simultaneous binding to cancer cells and immune cells. The two differential surfaces on the nanoparticle allow orthogonal functionalization with the anti-PD-1 antibody that interacts with the PD-1 receptor in cytotoxic T cells on the gold face and the pH Low Insertion Peptide (pHLIP), which undergoes specific insertion into the tumor cell membrane on the silica face. J-pHLIP-PD1 nanoparticles effectively bind the surface of tumor cells and capture T cells, facilitating the formation of immune synapse-like structures that lead to reduced cancer cell viability in vitro, associated with immunogenic cell death signatures. The therapeutic potential of J-pHLIP-PD1 is also demonstrated in an in vivo metastatic melanoma model, where treatment with J-pHLIP-PD1 produces a significant decrease in metastatic burden and increases T cell presence. The Janus nanosystem represents an attractive platform that expands the toolbox of immune-engaging strategies, offering a flexible alternative to conventional immunotherapies that link immune and tumor cells, restoring cell-cell communication for cancer elimination
Beschreibung:Date Revised 24.09.2025
published: Print-Electronic
Citation Status Publisher
ISSN:1521-4095
DOI:10.1002/adma.202418838