Protein Toxin Chaperoned by LRP‐1‐Targeted Virus‐Mimicking Vesicles Induces High‐Efficiency Glioblastoma Therapy In Vivo

Jiang, Yu; Yang, Weijing; Zhang, Jian; Meng, Fenghua; Zhong, Zhiyuan

doi:10.1002/adma.201800316

Cited by 137 publications

(100 citation statements)

References 72 publications

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“…In line with our findings, Chu et al investigated the effect of Tet1 ligand density in neuronal cell uptake and concluded that lower densities of ligand resulted in improved internalization of HPMA-oligolysine copolymer NPs [241]. This could be explained by the fact that the excessive targeting ligand density can result in reduced selectivity, as steric hindrances can be formed due to the over proximity between ligands, decreasing their binding ability to neuronal cells and enhancing the binding to non-targeted cells [242]. Hence, it is important to optimize the NPs' ligand density to enhance targeting efficiency.…”

Section: Targeting Ligands Dilemmas In Neurospecific Deliverysupporting

confidence: 89%

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

et al. 2020

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Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.

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Section: Targeting Ligands Dilemmas In Neurospecific Deliverysupporting

confidence: 89%

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

et al. 2020

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“…These approaches can be categorized into the following two strategies: tight junction disruption and active passage through the vascular wall by targeting biomarkers expressed on brain endothelial cells. Several ligands have been reported to bind with endothelial markers for crossing the BBB, for example, rabies virus glycoprotein (RVG) binds to the acetylcholine receptor (AchR), Tf peptide bind to TfRs,17b angiopep‐2 binds to low‐density lipoprotein receptor‐related protein‐1 (LRP‐1), and GLUT1 antibody scFv bind to GLUT1 …”

Section: Targeting Strategies With Ligand‐installed Nanocarriersmentioning

confidence: 99%

Ligand‐Installed Nanocarriers toward Precision Therapy

2019

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Development of drug‐delivery systems that selectively target neoplastic cells has been a major goal of nanomedicine. One major strategy for achieving this milestone is to install ligands on the surface of nanocarriers to enhance delivery to target tissues, as well as to enhance internalization of nanocarriers by target cells, which improves accuracy, efficacy, and ultimately enhances patient outcomes. Herein, recent advances regarding the development of ligand‐installed nanocarriers are introduced and the effect of their design on biological performance is discussed. Besides academic achievements, progress on ligand‐installed nanocarriers in clinical trials is presented, along with the challenges faced by these formulations. Lastly, the future perspectives of ligand‐installed nanocarriers are discussed, with particular emphasis on their potential for emerging precision therapies.

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“…However, none of these methods were used for delivery of saporin-based constructs. The problem of BBB permeability for saporin-containing toxins was addressed in recent studies [146,147] where the authors used angiopep-2-directed and redox-responsive virus-mimicking polymersomes (angiopep-2 is a peptide targeting to low-density lipoprotein receptor-related protein-1) or apolipoprotein E peptide [(LRKLRKRLL)2C], which specifically binds to low-density lipoprotein receptor members. It was shown that these two approaches can efficiently and selectively chaperone saporin to orthotopic human glioblastoma xenografts in nude mice after systemic administration.…”

Section: Discussionmentioning

confidence: 99%

Saporin from Saponaria officinalis as a Tool for Experimental Research, Modeling, and Therapy in Neuroscience

Bolshakov

Stepanichev

Dobryakova

et al. 2020

Toxins

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Saporin, which is extracted from Saponaria officinalis, is a protein toxin that inactivates ribosomes. Saporin itself is non-selective toxin but acquires high specificity after conjugation with different ligands such as signaling peptides or antibodies to some surface proteins expressed in a chosen cell subpopulation. The saporin-based conjugated toxins were widely adopted in neuroscience as a convenient tool to induce highly selective degeneration of desired cell subpopulation. Induction of selective cell death is one of approaches used to model neurodegenerative diseases, study functions of certain cell subpopulations in the brain, and therapy. Here, we review studies where saporin-based conjugates were used to analyze cell mechanisms of sleep, general anesthesia, epilepsy, pain, and development of Parkinson’s and Alzheimer’s diseases. Limitations and future perspectives of use of saporin-based toxins in neuroscience are discussed.

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Protein Toxin Chaperoned by LRP‐1‐Targeted Virus‐Mimicking Vesicles Induces High‐Efficiency Glioblastoma Therapy In Vivo

Cited by 137 publications

References 72 publications

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Ligand‐Installed Nanocarriers toward Precision Therapy

Saporin from Saponaria officinalis as a Tool for Experimental Research, Modeling, and Therapy in Neuroscience

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