Photodynamic therapy (PDT) represents an emerging strategy to treat various malignancies, including colorectal cancer (CC), the third most common cancer type. This work presents an engineered M13 phage retargeted towards CC cells through pentavalent display of a disulfide-constrained peptide nonamer. The M13CC nanovector was conjugated with the photosensitizer Rose Bengal (RB), and the photodynamic anticancer effects of the resulting M13CC-RB bioconjugate were investigated on CC cells. We show that upon irradiation M13CC-RB is able to impair CC cell viability, and that this effect depends on i) photosensitizer concentration and ii) targeting efficiency towards CC cell lines, proving the specificity of the vector compared to unmodified M13 phage. We also demonstrate that M13CC-RB enhances generation and intracellular accumulation of reactive oxygen species (ROS) triggering CC cell death. To further investigate the anticancer potential of M13CC-RB, we performed PDT experiments on 3D CC spheroids, proving, for the first time, the ability of engineered M13 phage conjugates to deeply penetrate multicellular spheroids. Moreover, significant photodynamic effects, including spheroid disruption and cytotoxicity, were readily triggered at picomolar concentrations of the phage vector. Taken together, our results promote engineered M13 phages as promising nanovector platform for targeted photosensitization, paving the way to novel adjuvant approaches to fight CC malignancies.

Molecular engineering of a spheroid-penetrating phage nanovector for photodynamic treatment of colon cancer cells / Turrini, Eleonora; Ulfo, Luca; Costantini, Paolo Emidio; Saporetti, Roberto; Di Giosia, Matteo; Nigro, Michela; Petrosino, Annapaola; Pappagallo, Lucia; Kaltenbrunner, Alena; Cantelli, Andrea; Pellicioni, Valentina; Catanzaro, Elena; Fimognari, Carmela; Calvaresi, Matteo; Danielli, Alberto. - In: CELLULAR AND MOLECULAR LIFE SCIENCES. - ISSN 1420-682X. - ELETTRONICO. - 81:1(2024), pp. 143-160. [10.1007/s00018-024-05174-7]

Molecular engineering of a spheroid-penetrating phage nanovector for photodynamic treatment of colon cancer cells

Turrini, Eleonora
Co-primo
;
Ulfo, Luca
Co-primo
;
Costantini, Paolo Emidio
Co-primo
;
Saporetti, Roberto;Di Giosia, Matteo;Nigro, Michela;Petrosino, Annapaola;Pappagallo, Lucia;Kaltenbrunner, Alena;Cantelli, Andrea;Pellicioni, Valentina;Catanzaro, Elena;Fimognari, Carmela;Calvaresi, Matteo
;
Danielli, Alberto
2024

Abstract

Photodynamic therapy (PDT) represents an emerging strategy to treat various malignancies, including colorectal cancer (CC), the third most common cancer type. This work presents an engineered M13 phage retargeted towards CC cells through pentavalent display of a disulfide-constrained peptide nonamer. The M13CC nanovector was conjugated with the photosensitizer Rose Bengal (RB), and the photodynamic anticancer effects of the resulting M13CC-RB bioconjugate were investigated on CC cells. We show that upon irradiation M13CC-RB is able to impair CC cell viability, and that this effect depends on i) photosensitizer concentration and ii) targeting efficiency towards CC cell lines, proving the specificity of the vector compared to unmodified M13 phage. We also demonstrate that M13CC-RB enhances generation and intracellular accumulation of reactive oxygen species (ROS) triggering CC cell death. To further investigate the anticancer potential of M13CC-RB, we performed PDT experiments on 3D CC spheroids, proving, for the first time, the ability of engineered M13 phage conjugates to deeply penetrate multicellular spheroids. Moreover, significant photodynamic effects, including spheroid disruption and cytotoxicity, were readily triggered at picomolar concentrations of the phage vector. Taken together, our results promote engineered M13 phages as promising nanovector platform for targeted photosensitization, paving the way to novel adjuvant approaches to fight CC malignancies.
2024
Molecular engineering of a spheroid-penetrating phage nanovector for photodynamic treatment of colon cancer cells / Turrini, Eleonora; Ulfo, Luca; Costantini, Paolo Emidio; Saporetti, Roberto; Di Giosia, Matteo; Nigro, Michela; Petrosino, Annapaola; Pappagallo, Lucia; Kaltenbrunner, Alena; Cantelli, Andrea; Pellicioni, Valentina; Catanzaro, Elena; Fimognari, Carmela; Calvaresi, Matteo; Danielli, Alberto. - In: CELLULAR AND MOLECULAR LIFE SCIENCES. - ISSN 1420-682X. - ELETTRONICO. - 81:1(2024), pp. 143-160. [10.1007/s00018-024-05174-7]
Turrini, Eleonora; Ulfo, Luca; Costantini, Paolo Emidio; Saporetti, Roberto; Di Giosia, Matteo; Nigro, Michela; Petrosino, Annapaola; Pappagallo, Lucia; Kaltenbrunner, Alena; Cantelli, Andrea; Pellicioni, Valentina; Catanzaro, Elena; Fimognari, Carmela; Calvaresi, Matteo; Danielli, Alberto
File in questo prodotto:
File Dimensione Formato  
s00018-024-05174-7.pdf

accesso aperto

Descrizione: Turrini_Ulfo_Costantini_etal_CMLS2024
Tipo: Versione (PDF) editoriale
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 4.07 MB
Formato Adobe PDF
4.07 MB Adobe PDF Visualizza/Apri
18_2024_5174_MOESM1_ESM (1).docx

accesso aperto

Descrizione: SupplementaryMaterial_Turrini_CMLS2024
Tipo: File Supplementare
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione (CCBY)
Dimensione 1.09 MB
Formato Microsoft Word XML
1.09 MB Microsoft Word XML Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/966465
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact