Orthogonal nanoarchitectonics of M13 phage for receptor targeted anticancer photodynamic therapy

Ulfo, Luca; Cantelli, Andrea; Petrosino, Angelo; Costantini, Paolo Emidio; Nigro, Maria Concetta; Starinieri, Francesco; Turrini, Eleonora; Zadran, Suleman Khan; Zuccheri, Giampaolo; Saporetti, Roberto; Giosia, Matteo Di; Danielli, Alberto; Calvaresi, Matteo

doi:10.1039/d1nr06053h

Cited by 29 publications

(38 citation statements)

References 79 publications

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“…Upon laser irradiation (660 nm, irradiance 50 mW/cm 2 ), this new phage platform was able to generate ROS via the type I mechanism and to kill SKOV3 and COV362 ovarian cancer cells, even at concentrations at which Ce6 alone was ineffective. As also reported for the phage-RB conjugates [248], further microscopic analysis showed an enhanced cellular uptake of phage-Ce6 conjugates compared to free Ce6 and their mitochondrial localization. Following irradiation, autophagy induction was detected in target cells, supporting the outstanding nanobiotechnological potential of M13 for receptortargeted PDT of EGFR-positive ovarian cancer.…”

Section: Refactored Anti-egfr Phagessupporting

confidence: 81%

“…Ulfo et al (Table 16) recently took a fully orthogonal approach to M13 to target EGFR-overexpressing tumor cells [248]. A short EGFR-targeting peptide (SYPIPDT) identified from the screening of a phage display peptide library [250] was genetically displayed in pentavalency at the phage tip, while the major pVIII capsomers were chemically conjugated with hundreds of Rose Bengal photosensitizers.…”

Section: Refactored Anti-egfr Phagesmentioning

confidence: 99%

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EGFR-Targeted Photodynamic Therapy

et al. 2022

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The epidermal growth factor receptor (EGFR) plays a pivotal role in the proliferation and metastatization of cancer cells. Aberrancies in the expression and activation of EGFR are hallmarks of many human malignancies. As such, EGFR-targeted therapies hold significant potential for the cure of cancers. In recent years, photodynamic therapy (PDT) has gained increased interest as a non-invasive cancer treatment. In PDT, a photosensitizer is excited by light to produce reactive oxygen species, resulting in local cytotoxicity. One of the critical aspects of PDT is to selectively transport enough photosensitizers to the tumors environment. Accordingly, an increasing number of strategies have been devised to foster EGFR-targeted PDT. Herein, we review the recent nanobiotechnological advancements that combine the promise of PDT with EGFR-targeted molecular cancer therapy. We recapitulate the chemistry of the sensitizers and their modes of action in PDT, and summarize the advantages and pitfalls of different targeting moieties, highlighting future perspectives for EGFR-targeted photodynamic treatment of cancer.

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Section: Refactored Anti-egfr Phagessupporting

confidence: 81%

Section: Refactored Anti-egfr Phagesmentioning

confidence: 99%

EGFR-Targeted Photodynamic Therapy

et al. 2022

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“…This evidence points out the usefulness of HSA formulation for chemotherapeutic drugs and mTHPC@HSA perfectly fits in this context. Moreover, the performances of the mTHPC@HSA platform can be additionally improved by using light-harvesting antennae to extend the PDT activity of the mTHPC into the NIR [66], or by attaching targeting moieties to specifically address cellular receptors that are usually overexpressed in cancer cells for receptor-targeted PDT [67][68][69][70][71].…”

Section: Discussionmentioning

confidence: 99%

Carrying Temoporfin with Human Serum Albumin: A New Perspective for Photodynamic Application in Head and Neck Cancer

et al. 2022

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Temoporfin (mTHPC) is approved in Europe for the photodynamic treatment of head and neck squamous cell carcinoma (HNSCC). Although it has a promising profile, its lipophilic character hampers the full exploitation of its potential due to high tendency of aggregation and a reduced ROS generation that compromise photodynamic therapy (PDT) efficacy. Moreover, for its clinical administration, mTHPC requires the presence of ethanol and propylene glycol as solvents, often causing adverse effects in the site of injection. In this paper we explored the efficiency of a new mTHPC formulation that uses human serum albumin (HSA) to disperse the photosensitizer in solution (mTHPC@HSA), investigating its anticancer potential in two HNSCC cell lines. Through a comprehensive characterization, we demonstrated that mTHPC@HSA is stable in physiological environment, does not aggregate, and is extremely efficient in PDT performance, due to its high singlet oxygen generation and the high dispersion as monomolecular form in HSA. This is supported by the computational identification of the specific binding pocket of mTHPC in HSA. Moreover, mTHPC@HSA-PDT induces cytotoxicity in both HNSCC cell lines, increasing intracellular ROS generation and the number of γ-H2AX foci, a cellular event involved in the global response to cellular stress. Taken together these results highlight the promising phototoxic profile of the complex, prompting further studies to assess its clinical potential.

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“…In addition, theoretical considerations indicate that phage relaxivity should increase at lower fields (due to slowing down of molecular tumbling), which could also contribute to enhancing contrast at clinically-relevant field strengths (e.g., 1.5 Tesla), albeit with a tradeoff in overall signal intensity. In summary, as a phage-based molecular probe for visualizing targeted bacterial strains with MRI, we envision a synergy in the development of DP1-phage technology with rapidly evolving advances in emerging biotherapeutic platforms involving the use of live microorganisms as well as bacteriophage formulations for noninvasive diagnostics and treatment of diseases like cancer [46][47][48][49][50][51][52] , inflammatory conditions 53,54 , metabolic disorders 55,56 , and antibioticresistant infections [57][58][59][60][61] .…”

Section: Discussionmentioning

confidence: 99%

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

Borg

Ozbakir

et al. 2022

Preprint

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The ability to noninvasively detect bacteria at any depth inside opaque tissues has important applications ranging from infection diagnostics to tracking therapeutic microbes in their mammalian host. Current examples of probes for detecting bacteria with strain-type specificity are largely based on optical dyes, which cannot be used to examine bacteria in deep tissues due to the physical limitation of light scattering. Here, we describe a new biomolecular probe for visualizing bacteria in a cell-type specific fashion using magnetic resonance imaging (MRI). The probe is based on a peptide that selectively binds manganese and is attached in high numbers to the capsid of filamentous phage. By genetically engineering phage particles to display this peptide, we are able to bring manganese ions to specific bacterial cells targeted by the phage, thereby producing MRI contrast. We show that this approach allows MRI-based detection of targeted E. coli strains while discriminating against non-target bacteria as well as mammalian cells. By engineering the phage coat to display a protein that targets cell surface receptors in V. cholerae, we further show that this approach can be applied to image other bacterial targets with MRI. Finally, as a preliminary example of in vivo applicability, we demonstrate MR imaging of phage-labeled V. cholerae cells implanted subcutaneously in mice. The nanomaterial developed here thus represents a path towards noninvasive detection and tracking of bacteria by combining the programmability of phage architecture with the ability to produce three-dimensional images of biological structures at any arbitrary depth with MRI.

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Orthogonal nanoarchitectonics of M13 phage for receptor targeted anticancer photodynamic therapy

Abstract: Not all viruses are bad. We developed an orthogonal approach (genetic/chemical) to engineer M13 bacteriophages as targeted vectors for efficient photodynamic killing of cancer cells.

Cited by 29 publications

References 79 publications

EGFR-Targeted Photodynamic Therapy

EGFR-Targeted Photodynamic Therapy

Carrying Temoporfin with Human Serum Albumin: A New Perspective for Photodynamic Application in Head and Neck Cancer

A genetically engineered phage-based nanomaterial for detecting bacteria with magnetic resonance imaging

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