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A Photoactive Supramolecular Complex Targeting PD-L1 Reveals a Weak Correlation between Photoactivation Efficiency and Receptor Expression Levels in Non-Small-Cell Lung Cancer Tumor Models.
Delcanale, Pietro; Alampi, Manuela Maria; Mussini, Andrea; Fumarola, Claudia; Galetti, Maricla; Petronini, Pier Giorgio; Viappiani, Cristiano; Bruno, Stefano; Abbruzzetti, Stefania.
Afiliação
  • Delcanale P; Department of Mathematical, Physical and Computer Sciences, University of Parma, 43124 Parma, Italy.
  • Alampi MM; Department of Mathematical, Physical and Computer Sciences, University of Parma, 43124 Parma, Italy.
  • Mussini A; Department of Mathematical, Physical and Computer Sciences, University of Parma, 43124 Parma, Italy.
  • Fumarola C; Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy.
  • Galetti M; Department of Occupational and Environmental Medicine, Epidemiology and Hygiene, INAIL-Italian Workers' Compensation Authority, 00078 Rome, Italy.
  • Petronini PG; Department of Medicine and Surgery, University of Parma, 43125 Parma, Italy.
  • Viappiani C; Department of Mathematical, Physical and Computer Sciences, University of Parma, 43124 Parma, Italy.
  • Bruno S; Department of Food and Drug, University of Parma, 43124 Parma, Italy.
  • Abbruzzetti S; Department of Mathematical, Physical and Computer Sciences, University of Parma, 43124 Parma, Italy.
Pharmaceutics ; 15(12)2023 Dec 14.
Article em En | MEDLINE | ID: mdl-38140116
ABSTRACT
Photo-immunotherapy uses antibodies conjugated to photosensitizers to produce nanostructured constructs endowed with targeting properties and photo-inactivation capabilities towards tumor cells. The superficial receptor density on cancer cells is considered a determining factor for the efficacy of the photodynamic treatment. In this work, we propose the use of a photoactive conjugate that consists of the clinical grade PD-L1-binding monoclonal antibody Atezolizumab, covalently linked to either the well-known photosensitizer eosin or the fluorescent probe Alexa647. Using single-molecule localization microscopy (direct stochastic optical reconstruction microscopy, dSTORM), and an anti-PD-L1 monoclonal antibody labelled with Alexa647, we quantified the density of PD-L1 receptors exposed on the cell surface in two human non-small-cell lung cancer lines (H322 and A549) expressing PD-L1 to a different level. We then investigated if this value correlates with the effectiveness of the photodynamic treatment. The photodynamic treatment of H322 and A549 with the photo-immunoconjugate demonstrated its potential for PDT treatments, but the efficacy did not correlate with the PD-L1 expression levels. Our results provide additional evidence that receptor density does not determine a priori the level of photo-induced cell death.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceutics Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: Pharmaceutics Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Itália