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Targeting the senescent surfaceome through DPP4 antibody-functionalized nanoparticles. An application to cancer
Blanca Escriche-Navarro1, Eva Garrido2, Andrea Escudero3
1Instituto Interuniversitario de Investigación de Reconocimiento Molecular y Desarrollo Tecnológico (IDM) Universitat Politècnica de València, Universitat de València, Camino de Vera, s/n, 46022, Valencia, Spain; Unidad Mixta UPV-CIPF de Investigación en Mecanismos de Enfermedades y Nanomedicina, Universitat Politècnica de València, Centro de Investigación Príncipe Felipe, C/ Eduardo Primo Yúfera 3, 46012, Valencia, Spain; CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Av. Monforte de Lemos, 3-5. Pabellón 11. Planta 0, 28029, Madrid, Spain; Unidad Mixta de Investigación en Nanomedicina y Sensores, Universitat Politècnica de València, IIS La Fe. Av. Fernando Abril Martorell, 106 Torre A 7(a) Planta, 46026, Valencia, Spain.
Researchers developed a novel nanoparticle to target senescent melanoma cells by identifying dipeptidyl peptidase 4 (DPP4) as a senescence biomarker. This targeted approach effectively eliminates senescent cells and reduces tumor growth, offering a promising senolytic therapy.
Area of Science:
- Biomedical Engineering
- Oncology
- Cell Biology
Background:
- Targeting senescent cells (senolytics) faces challenges due to heterogeneous phenotypes and lack of universal biomarkers.
- Current senolytic strategies are limited by off-target effects and toxicity, hindering clinical application.
Purpose of the Study:
- To develop a targeted nanoparticle for eliminating senescent cancer cells.
- To identify and utilize dipeptidyl peptidase 4 (DPP4) as a biomarker for senescent cells.
Main Methods:
- Senescence was induced in human melanoma cells using palbociclib.
- A mesoporous silica nanoparticle was designed, loaded with navitoclax, and functionalized with anti-DPP4 antibodies.
- In vitro and in vivo studies in a mouse model were conducted to evaluate nanoparticle efficacy.
Main Results:
- Palbociclib-induced senescence in melanoma cells showed overexpression of DPP4.
- The DPP4-targeted nanoparticles selectively detected and eliminated senescent cells.
- Nanoparticle treatment effectively reduced tumor growth in vivo.
Conclusions:
- DPP4 is a viable biomarker for targeting senescent cells in melanoma.
- Surfaceome-targeted nanoparticles offer a promising strategy for improving senolytic therapy.
- This approach demonstrates potential for enhanced senolytic efficacy with reduced toxicity.
