Pyruvate-conjugation of PEGylated liposomes for targeted drug delivery to retinal photoreceptors

Christensen, Gustav; Chen, Yiyi; Urimi, Dileep; Zizmare, Laimdota; Trautwein, Christoph; Schipper, Nicolaas; Paquet-Durand, François

doi:10.1016/j.biopha.2023.114717

Cited by 3 publications

(1 citation statement)

References 48 publications

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“…The functional diversity of polymers, including POx, has inspired different targeting or stimuli-responsive mechanisms ,,− for efficient drug delivery. Active targeting groups can be attached to functional polymer handles, allowing the enrichment of polymeric DDS to the site of diseased tissues. − For brain delivery, polymeric DDS have been modified with different surface chemistries to target cell transport mechanisms, such as nutrient transporter pathways (GLUT, LAT, MCT), receptor-mediated transcytosis (transferrin, insulin), absorptive-mediated transcytosis (charge, albumin), or cell-mediated transcytosis. − To date, there are limited studies of DDS targeting nutrient transporter pathways, specifically monocarboxylate transporter system 1 (MCT1), for enhanced cellular uptake. − …”

Section: Introductionmentioning

confidence: 99%

Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models

Morrow,

Mazrad,

Warne

et al. 2024

Biomacromolecules

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A great deal of nanocarriers have been applied to induce ferroptosis in cancer research, yet there are limited examples of nanocarrier formulations to rescue ferroptosis, which can be applied to neurodegeneration, inflammation, liver damage, kidney disease, and more. Here, we present the synthesis, characterization, and in vitro evaluation of pH-responsive, core-cross-linked micelle (CCM) ferrostatin-1 (Fer-1) conjugates with amine, valproic acid, and biotin surface chemistries. Fer-1 release from stable and defined CCM Fer-1 conjugates was quantified, highlighting the sustained release for 24 h. CCM Fer-1 conjugates demonstrated excellent ferroptosis rescue by their antilipid peroxidation activity in a diverse set of cell lines in vitro. Additionally, CCMs showed tunable cell association in SH-SY5Y and translocation across an in vitro blood–brain barrier (BBB) model, highlighting potential brain disease applications. Overall, here, we present a polymeric Fer-1 delivery system to enhance Fer-1 action, which could help in improving Fer-1 action in the treatment of ferroptosis-related diseases.

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Section: Introductionmentioning

confidence: 99%

Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models

Morrow,

Mazrad,

Warne

et al. 2024

Biomacromolecules

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Long-term HIF-1α stabilization reduces respiration, promotes mitophagy, and results in retinal cell death

Nsiah,

Morgan,

Donkor

et al. 2023

Sci Rep

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Ocular hypertension during glaucoma can lead to hypoxia, activation of the HIF transcription factors, and a metabolic shift toward glycolysis. This study aims to test whether chronic HIF activation and the attendant metabolic reprogramming can initiate glaucoma-associated pathology independently of ocular hypertension. HIF-1α stabilization was induced in mice for 2 and 4 weeks by inhibiting prolyl hydroxylases using the small molecule Roxadustat. HIF-1α stabilization and the expression of its downstream bioenergetic targets were investigated in the retina by immunofluorescence, capillary electrophoresis, and biochemical enzyme activity assays. Roxadustat dosing resulted in significant stabilization of HIF-1α in the retina by 4 weeks, and upregulation in glycolysis-associated proteins (GLUT3, PDK-1) and enzyme activity in both neurons and glia. Accordingly, succinate dehydrogenase, mitochondrial marker MTCO1, and citrate synthase activity were significantly decreased at 4 weeks, while mitophagy was significantly increased. TUNEL assay showed significant apoptosis of cells in the retina, and PERG amplitude was significantly decreased with 4 weeks of HIF-1α stabilization. A significant increase in AMPK activation and glial hypertrophy, concomitant with decreases in retinal ganglion cell function and inner retina cell death suggests that chronic HIF-1α stabilization alone is detrimental to retina metabolic homeostasis and cellular survival.

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Next-Generation Nanomedicine Approaches for the Management of Retinal Diseases

Mahaling

Low

et al. 2023

Pharmaceutics

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Retinal diseases are one of the leading causes of blindness globally. The mainstay treatments for these blinding diseases are laser photocoagulation, vitrectomy, and repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF) or steroids. Unfortunately, these therapies are associated with ocular complications like inflammation, elevated intraocular pressure, retinal detachment, endophthalmitis, and vitreous hemorrhage. Recent advances in nanomedicine seek to curtail these limitations, overcoming ocular barriers by developing non-invasive or minimally invasive delivery modalities. These modalities include delivering therapeutics to specific cellular targets in the retina, providing sustained delivery of drugs to avoid repeated intravitreal injections, and acting as a scaffold for neural tissue regeneration. These next-generation nanomedicine approaches could potentially revolutionize the treatment landscape of retinal diseases. This review describes the availability and limitations of current treatment strategies and highlights insights into the advancement of future approaches using next-generation nanomedicines to manage retinal diseases.

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Pyruvate-conjugation of PEGylated liposomes for targeted drug delivery to retinal photoreceptors

Cited by 3 publications

References 48 publications

Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models

Schiff-Base Cross-Linked Poly(2-oxazoline) Micelle Drug Conjugates Possess Antiferroptosis Activity in Numerous In Vitro Cell Models

Long-term HIF-1α stabilization reduces respiration, promotes mitophagy, and results in retinal cell death

Next-Generation Nanomedicine Approaches for the Management of Retinal Diseases

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