Flexible synthesis of cationic peptide–porphyrin derivatives for light-triggered drug delivery and photodynamic therapy

Dondi, Ruggero; Yaghini, Elnaz; Tewari, Kunal; Wang, L.; Giuntini, Francesca; Loizidou, Marilena; MacRobert, Alexander J.; Eggleston, Ian M.

doi:10.1039/c6ob02135b

Cited by 32 publications

(54 citation statements)

References 49 publications

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“…Peptide 6 was obtained by N-terminal derivatisation of the resin-bound Tat (48–57) sequence with 11-azidoundecanoic acid using HATU activation 28 .…”

Section: Methodsmentioning

confidence: 99%

Endolysosomal targeting of a clinical chlorin photosensitiser for light-triggered delivery of nano-sized medicines

Yaghini

Dondi

Tewari

et al. 2017

Sci Rep

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A major problem with many promising nano-sized biotherapeutics including macromolecules is that owing to their size they are subject to cellular uptake via endocytosis, and become entrapped and then degraded within endolysosomes, which can significantly impair their therapeutic efficacy. Photochemical internalisation (PCI) is a technique for inducing cytosolic release of the entrapped agents that harnesses sub-lethal photodynamic therapy (PDT) using a photosensitiser that localises in endolysosomal membranes. Using light to trigger reactive oxygen species-mediated rupture of the photosensitised endolysosomal membranes, the spatio-temporal selectivity of PCI then enables cytosolic release of the agents at the selected time after administration so that they can reach their intracellular targets. However, conventional photosensitisers used clinically for PDT are ineffective for photochemical internalisation owing to their sub-optimal intracellular localisation. In this work we demonstrate that such a photosensitiser, chlorin e6, can be repurposed for PCI by conjugating the chlorin to a cell penetrating peptide, using bioorthogonal ligation chemistry. The peptide conjugation enables targeting of endosomal membranes so that light-triggered cytosolic release of an entrapped nano-sized cytotoxin can be achieved with consequent improvement in cytotoxicity. The photoproperties of the chlorin moiety are also conserved, with comparable singlet oxygen quantum yields found to the free chlorin.

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“…Peptide 6 was obtained by N-terminal derivatisation of the resin-bound Tat (48–57) sequence with 11-azidoundecanoic acid using HATU activation 28 .…”

Section: Methodsmentioning

confidence: 99%

Endolysosomal targeting of a clinical chlorin photosensitiser for light-triggered delivery of nano-sized medicines

Yaghini

Dondi

Tewari

et al. 2017

Sci Rep

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“…Many functional peptide libraries have actually been described in the literature, with different sequences and functions, offering a versatile platform of delivery agents to localize PS conjugates in different kinds of cells and tissues. 48 Covalently linked PS-peptide biohybrids can be synthesized, taking advantage of mild synthetic organic methodologies such as amide [49][50][51][52][53]77,78,81,[85][86][87]89,[91][92][93]95,97,104,105 or sulphonamide 54 bond formation, palladium-catalysed cross-coupling reactions, 55,56 click-chemistry reactions [57][58][59]81,94 and isothiocyanate chemistry, 60,82 among other strategies. Supramolecular approaches have also been used toward self-assembled peptide nanofibers, 61 nanodots, 62 vesicles, 63 light harvesting complexes, 64 arrays 65 or polymeric micelles with a peptide-decorated surface, 66 among others.…”

Section: Conjugation Of Ps To Short Peptide Sequencesmentioning

confidence: 99%

Porphyrinoid biohybrid materials as an emerging toolbox for biomedical light management

et al. 2018

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The development of photoactive and biocompatible nanomaterials is a current major challenge of materials science and nanotechnology, as they will contribute to promoting current and future biomedical applications. A growing strategy in this direction consists of using biologically inspired hybrid materials to maintain or even enhance the optical properties of chromophores and fluorophores in biological media. Within this area, porphyrinoids constitute the most important family of organic photosensitizers. The following extensive review will cover their incorporation into different kinds of photosensitizing biohybrid materials, as a fundamental research effort toward the management of light for biomedical use, including technologies such as photochemical internalization (PCI), photoimmunotherapy (PIT), and theranostic combinations of fluorescence imaging and photodynamic therapy (PDT) or photodynamic inactivation (PDI) of microorganisms.

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“…In the past few decades, the rapid development of nanotechnology has brought new opportunities to improve the application of porphyrin-based PDT in vivo. There are three main reasons why nanotechnology is attractive in PDT: (1) targeting potential increases the concentration of the PS at the target site, which increases the accumulation of porphyrins in tumours, and reduces damage to normal tissues/cells; (2) nanoparticles (NPs) can improve the water solubility and light stability of hydrophobic PSs; and (3) NPs can maintain a constant rate of PS delivery at the desired sites due to zero-order release kinetics 141 . Nanoparticlemediated porphyrin delivery strategies include encapsulation (metal-organic frameworks 142 , polymeric micelles 143 , mesoporous silica nanoshells 144 ) covalent conjugation 145 , and self-assembly 146 .…”

Section: Nanotechnology and Nanochemistrymentioning

confidence: 99%

“…Despite tremendous efforts to develop modified nanosystems for effective PDT for cancer treatment, searching for a nanostructured drug delivery system based on surface-functionalised NPs that combine targeted molecular recognition of tumours with reactive singlet oxygen production by PSs under PDT irradiation remains a challenge. Such system would be considered to be biosafe in clinical settings and thus requires further investigation 141 .…”

Section: Nanotechnology and Nanochemistrymentioning

confidence: 99%

Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy

Lin

Zhou

Bai

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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With the development of photodynamic therapy (PDT), remarkable studies have been conducted to generate photosensitisers (PSs), especially porphyrin PSs. A variety of chemical modifications of the porphyrin skeleton have been introduced to improve cellular delivery, stability, and selectivity for cancerous tissues. This review aims to highlight the developments in porphyrin-based structural modifications, with a specific emphasis on the role of PDT in anticancer treatment and the design of PSs to achieve a synergistic effect on multiple targets.

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Flexible synthesis of cationic peptide–porphyrin derivatives for light-triggered drug delivery and photodynamic therapy

Abstract: Amphiphilic cell-penetrating peptide–porphyrin conjugates have been developed for application in light-based therapeutic techniques.

Cited by 32 publications

References 49 publications

Endolysosomal targeting of a clinical chlorin photosensitiser for light-triggered delivery of nano-sized medicines

Endolysosomal targeting of a clinical chlorin photosensitiser for light-triggered delivery of nano-sized medicines

Porphyrinoid biohybrid materials as an emerging toolbox for biomedical light management

Chemical approaches for the enhancement of porphyrin skeleton-based photodynamic therapy

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