Permeability of PEGylated Immunoarsonoliposomes Through In Vitro Blood Brain Barrier-Medulloblastoma Co-culture Models for Brain Tumor Therapy

Al-Shehri, Abdulghani; Favretto, Marco E.; Ioannou, Panayiotis V.; Romero, Ignacio A.; Couraud, Pierre‐Olivier; Weksler, Babette B.; Parker, Terry L.; Kallinteri, Paraskevi

doi:10.1007/s11095-014-1519-8

Cited by 21 publications

(7 citation statements)

References 34 publications

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“…We further compared the permeability of IL13-conjugated NPs to NPs conjugated with transferrin (Tf), as a gold standard of BBB targeting molecules. [39,40] The permeability value obtained here for Tf-PEG-NPs (≈12.3 × 10 −7 cm s −1 ) was also in the range of previously reported values for Tfconjugated carriers (7.5−35 × 10 −7 cm s −1 ), [28,37,38] and more importantly, was comparable to that of our IL13-PEG-NPs. This result supports the prior literature findings and demonstrates that IL13 conjugation offers an effective strategy for transport across the BBB.…”

Section: In Vitro Bbb Transport Studiessupporting

confidence: 89%

Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation

Kang

Holley

Abidian

et al. 2020

Adv Healthcare Materials

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The limited effectiveness of current therapeutics against malignant brain gliomas has led to an urgent need for development of new formulations against these tumors. Chelator Dp44mT (di‐2‐pyridylketone‐4,4‐dimethyl‐3‐thiosemicarbazone) presents a promising candidate to defeat gliomas due to its exceptional anti‐tumor activity and its unique ability to overcome multidrug resistance. The goal of this study is to develop a targeted nano‐carrier for Dp44mT delivery to glioma tumors and to assess its therapeutic efficacy in vitro and in vivo. Dp44mT is loaded into poly(ethylene glycol) (PEG)ylated poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles (NPs) decorated with glioma‐targeting ligand Interlukin 13 (IL13). IL13‐conjugation enhanced the NP uptake by glioma cells and also improved their transport across an in vitro blood‐brain‐barrier (BBB) model. This targeted formulation showed an outstanding toxicity towards glioma cell lines and patient‐derived stem cells in vitro, with IC50 values less than 125 nM, and caused no significant death in healthy brain microvascular endothelial cells. In vivo, when tested on a xenograft mouse model, IL13‐conjugated Dp44mT‐NPs reduced the glioma tumor growth by ≈62% while their untargeted counterparts reduced the tumor growth by only ≈16%. Notably, this formulation does not cause any significant weight loss or kidney/liver toxicity in mice, demonstrating its great therapeutic potential.

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Section: In Vitro Bbb Transport Studiessupporting

confidence: 89%

Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation

Kang

Holley

Abidian

et al. 2020

Adv Healthcare Materials

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“…The hCMEC/D3 cell line has been developed as a model for the human BBB and has been used to test the permeability of several drugs (Al‐Shehri et al ., ; Ma et al ., ). Here, the results indicated that 62‐71‐3 ScFv was able to pass across the hCMEC/D3 cells whilst the 62‐71‐3 IgG was not.…”

Section: Discussionmentioning

confidence: 99%

Enhanced transport of plant‐produced rabies single‐chain antibody‐RVG peptide fusion protein across an in cellulo blood–brain barrier device

Phoolcharoen

Préhaud

Dolleweerd

et al. 2017

Plant Biotechnology Journal

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SummaryThe biomedical applications of antibody engineering are developing rapidly and have been expanded to plant expression platforms. In this study, we have generated a novel antibody molecule in planta for targeted delivery across the blood–brain barrier (BBB). Rabies virus (RABV) is a neurotropic virus for which there is no effective treatment after entry into the central nervous system. This study investigated the use of a RABV glycoprotein peptide sequence to assist delivery of a rabies neutralizing single‐chain antibody (ScFv) across an in cellulo model of human BBB. The 29 amino acid rabies virus peptide (RVG) recognizes the nicotinic acetylcholine receptor (nAchR) at neuromuscular junctions and the BBB. ScFv and ScFv‐RVG fusion proteins were produced in Nicotiana benthamiana by transient expression. Both molecules were successfully expressed and purified, but the ScFv expression level was significantly higher than that of ScFv‐RVG fusion. Both ScFv and ScFv‐RVG fusion molecules had potent neutralization activity against RABV in cellulo. The ScFv‐RVG fusion demonstrated increased binding to nAchR and entry into neuronal cells, compared to ScFv alone. Additionally, a human brain endothelial cell line BBB model was used to demonstrate that plant‐produced ScFv‐RVGP fusion could translocate across the cells. This study indicates that the plant‐produced ScFv‐RVGP fusion protein was able to cross the in cellulo BBB and neutralize RABV.

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“…For instance, RBE4 cell monolayers have been reported to produce permeability coefficients for sucrose of 214 x 10 -6 cms -1 (Rist et al, 1997) and permeability value of 195 x 10 -6 cms -1 was obtained with human brain capillary endothelial cell line (BB19) (Kusch-Poddar et al, 2005). Moreover, bEnd.3 monoculture sucrose value (96.1 ± 24.5 x 10 -6 cms -1 ) was comparable to hCMEC/D3, another immortalized human brain endothelial cell line, which was reported to have 80.7 x 10 -6 cms -1 for sucrose permeability (Al-Shehri et al, 2015).…”

Section: Discussionmentioning

confidence: 60%

Establishment of murinein vitroblood-brain barrier models using immortalized cell lines: co-cultures of brain endothelial cells, astrocytes, and neurons

Idris

Muharram

Zaini³

et al. 2018

Preprint

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Blood-brain barrier (BBB) is a selective barrier formed by the endothelial cells that line cerebral microvessels. It serves as a physical barrier due to the presence of complex tight junctions between adjacent endothelial cells which limits the paracellular movement of most molecules across the BBB. Many in vitro models of the BBB have been established to mimic these in vivo properties with limited success. In this study, we described the properties of a cell-based murine in vitro BBB model in five configurations constructed using immortalized cell lines in a 12-well format Transwell system: murine brain endothelial cells (bEnd.3) grown in a monoculture, or as co-culture in contact with astrocytes, or without contact with astrocytes or neurons, and triple coculture combining the three cell lines. We found that only contact and triple co-culture model closely mimic the in vivo BBB tightness as evaluated by apparent permeability (Papp) of sucrose and albumin producing the lowest Papp values of 0.56 ± 0.16 x 10 -6 cms -1 and 3.30 ± 0.51 x 10 -6 cms -1 , respectively, obtained in triple co-culture model. Co-culturing of bEnd.3 with astrocytes increased the expression of occludin as shown by western blot analysis, and immunohistochemistry showed an increase in peripheral localization of occludin and claudin-5.In addition, we found conditioned media were able to increase in vitro BBB model tightness through the modulation of tight junction proteins localization. We conclude that the presence of astrocytes and neurons in close proximity to brain endothelial cells is essential to produce a tight in vitro BBB model.

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Permeability of PEGylated Immunoarsonoliposomes Through In Vitro Blood Brain Barrier-Medulloblastoma Co-culture Models for Brain Tumor Therapy

Cited by 21 publications

References 34 publications

Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation

Tumor Targeted Delivery of an Anti‐Cancer Therapeutic: An In Vitro and In Vivo Evaluation

Enhanced transport of plant‐produced rabies single‐chain antibody‐RVG peptide fusion protein across an in cellulo blood–brain barrier device

Establishment of murinein vitroblood-brain barrier models using immortalized cell lines: co-cultures of brain endothelial cells, astrocytes, and neurons

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