Codelivery of a cytotoxin and photosensitiser<i>via</i>a liposomal nanocarrier: a novel strategy for light-triggered cytosolic release

Yaghini, Elnaz; Dondi, Ruggero; Edler, Karen J.; Loizidou, Marilena; MacRobert, Alexander J.; Eggleston, Ian M.

doi:10.1039/c8nr04048f

Cited by 23 publications

(18 citation statements)

References 62 publications

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“…PCI is a light-based method and is employed to trigger the endosomal escape of RIP. Saporin linked with a photosensitizer functionalized CPP showed cytotoxicity augmentation in MC28 fibrosarcoma cells [135]. Another study also showed that the cytotoxicity of IT 225.28-saporin was strengthened by using PCI with a photosensitizer disulfonated tetraphenyl chlorin (TPCS2a) [136].…”

Section: Perspectivesmentioning

confidence: 98%

Engineering of Ribosome-inactivating Proteins for Improving Pharmacological Properties

Lü

Zhu

Zheng

et al. 2020

Toxins

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Ribosome-inactivating proteins (RIPs) are N-glycosidases, which depurinate a specific adenine residue in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. This loop is important for anchoring elongation factor (EF-G for prokaryote or eEF2 for eukaryote) in mRNA translocation. Translation is inhibited after the attack. RIPs therefore may have been applied for anti-cancer, and anti-virus and other therapeutic applications. The main obstacles of treatment with RIPs include short plasma half-life, non-selective cytotoxicity and antigenicity. This review focuses on the strategies used to improve the pharmacological properties of RIPs on human immunodeficiency virus (HIV) and cancers. Coupling with polyethylene glycol (PEG) increases plasma time and reduces antigenicity. RIPs conjugated with antibodies to form immunotoxins increase the selective toxicity to target cells. The prospects for future development on the engineering of RIPs for improving their pharmacological properties are also discussed.

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Section: Perspectivesmentioning

confidence: 98%

Engineering of Ribosome-inactivating Proteins for Improving Pharmacological Properties

Lü

Zhu

Zheng

et al. 2020

Toxins

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“…Another approach to nanocarrier-assisted PCI was presented by Yaghini et al [148], where the authors used liposomes surface-functionalised with a cell penetrating peptide (CPP). The CPP had additionally a porphyrin moiety (meso-tetrakis tetraphenylporphyrin (TPP)-derivative) as the PS, conjugated to its N-terminus.…”

Section: Nanoparticle-mediated Pci As a Powerful Anticancer Drug Delimentioning

confidence: 99%

Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research

Jerjes¹,

Theodossiou

Hirschberg

et al. 2020

JCM

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Photochemical internalisation (PCI) is a unique intervention which involves the release of endocytosed macromolecules into the cytoplasmic matrix. PCI is based on the use of photosensitizers placed in endocytic vesicles that, following light activation, lead to rupture of the endocytic vesicles and the release of the macromolecules into the cytoplasmic matrix. This technology has been shown to improve the biological activity of a number of macromolecules that do not readily penetrate the plasma membrane, including type I ribosome-inactivating proteins (RIPs), gene-encoding plasmids, adenovirus and oligonucleotides and certain chemotherapeutics, such as bleomycin. This new intervention has also been found appealing for intracellular delivery of drugs incorporated into nanocarriers and for cancer vaccination. PCI is currently being evaluated in clinical trials. Data from the first-in-human phase I clinical trial as well as an update on the development of the PCI technology towards clinical practice is presented here.

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“…The drug delivery systems, both passively and actively, triggering the endolysosomal escape of the encapsulated substances have been developed in various studies with different mechanisms; for example, pH buffering/proton sponge, [5][6][7] osmotic pressure shock, 8 the flip-flop approach, 9 and photochemical/photophysical internalization. 10 The photochemical/photophysical internalization is defined by the incorporation of a photosensitive moiety into a carrier, and letting cargoes flee from the endolysosomes upon lightactivated chemical reactions and/or physical alterations. This light-triggering mechanism is spatially and time controllable.…”

Section: Introductionmentioning

confidence: 99%

<p>Inclusion of IR-820 into Soybean-Phosphatides-Based Nanoparticles for Near-Infrared-Triggered Release and Endolysosomal Escape in HaCaT Keratinocytes at Insignificant Cytotoxic Level</p>

Homsirikamol

Suvanasuthi

Viravaidya-Pasuwat

2020

IJN

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The degradation of drugs within endolysosomes has been widely addressed as a cause of poor bioavailability. One of the strategies to allow molecules to escape from a destructive fate is to introduce a photosensitizing moiety into a drug carrier enabling the permeabilization of endosomes and endolysosomes upon irradiation. This paper presents an alternative delivery nanosystem composed of cost-effective soybean phosphatides mixed with IR-820, a near-infrared (NIR) sensitizer, to load various active compounds and trigger an endolysosomal escape with a low cytotoxic effect. Methods: IR-820-incorporated phosphatides-based nanoparticles were formulated using a thinfilm hydration method to encapsulate different molecular probes and a drug model. The nanoparticles were characterized in vitro using dynamic light scattering, transmission electron microscopy, as well as ultraviolet-visible and fluorescence spectroscopy techniques. The NIR-corresponding generation of the photochemical products, the content release, and the cytotoxicity toward the HaCaT keratinocyte cell line were evaluated. The cellular internalization and endolysosomal escape were monitored using a cytochemical marker and fluorescent probes with a colocalization analysis. Results: The IR-820-combined nanoparticles revealed the NIR-triggered changes in the singlet oxygen presence, nanoparticle architecture, and release rate without being cytotoxic. Additionally, the nanoplatform appeared to enhance cellular uptake of the macromolecules. The localization of the cytochemical marker and the colocalization analysis on the fluorescence signals of the encapsulated fluorophore and the lysosome-labeling reporter implied the transient endolysosomal escape of the cargo within the HaCaT cells after NIR irradiation. Conclusion: The inclusion of IR-820 into a soybean-phosphatides base ingredient provides NIR responsiveness, particularly the endolysosomal escape of the payload, to the formulated nanoparticles, while preserving the beneficial properties as a drug carrier. This alternative delivery nanomedicine system has future potential to provide high bioavailability of cytosolic drugs utilizing time-and spatial-controllable NIR triggerability as well as the synergistic therapeutic effects with NIR-biomodulation.

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Codelivery of a cytotoxin and photosensitiserviaa liposomal nanocarrier: a novel strategy for light-triggered cytosolic release

Abstract: Light-triggered intracellular delivery of a protein toxin was achieved by codelivery via a liposomal nanocarrier, targeted with a cell-penetrating peptide (CPP)–photosensitiser conjugate.

Cited by 23 publications

References 62 publications

Engineering of Ribosome-inactivating Proteins for Improving Pharmacological Properties

Engineering of Ribosome-inactivating Proteins for Improving Pharmacological Properties

Photochemical Internalization for Intracellular Drug Delivery. From Basic Mechanisms to Clinical Research

<p>Inclusion of IR-820 into Soybean-Phosphatides-Based Nanoparticles for Near-Infrared-Triggered Release and Endolysosomal Escape in HaCaT Keratinocytes at Insignificant Cytotoxic Level</p>

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