Brain-Targeted Delivery of Docetaxel by Glutathione-Coated Nanoparticles for Brain Cancer

Grover, Aditya; Hirani, Anjali; Pathak, Yashwant; Sutariya, Vijaykumar

doi:10.1208/s12249-014-0165-0

Cited by 58 publications

(30 citation statements)

References 26 publications

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“…GSH receptors at the BBB interface offer an option in targeting these receptors by GSH-coated nanoparticles to escalate the active or passive transcytosis of therapeutic agents to the brain [12,13]. GSH-PEGylated liposomes have been effectively applied as a brain drug delivery platform for the improvement of numerous treatments.…”

Section: Discussionmentioning

confidence: 99%

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Enhancing Anticancer Effect of Gefitinib across the Blood–Brain Barrier Model Using Liposomes Modified with One α-Helical Cell-Penetrating Peptide or Glutathione and Tween 80

Lin¹,

Hong²,

Wang³

et al. 2016

IJMS

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Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI), such as gefitinib, have been demonstrated to effectively treat the patients of extracranial non-small cell lung cancer (NSCLC). However, these patients often develop brain metastasis (BM) during their disease course. The major obstacle to treat BM is the limited penetration of anticancer drugs across the blood–brain barrier (BBB). In the present study, we utilized gefitinib-loaded liposomes with different modifications to improve gefitinib delivery across the in vitro BBB model of bEnd.3 cells. Gefitinib was encapsulated in small unilamellar liposomes modified with glutathione (GSH) and Tween 80 (SUV-G+T; one ligand plus one surfactant) or RF (SUV-RF; one α-helical cell-penetrating peptide). GSH, Tween 80, and RF were tested by the sulforhodamine B (SRB) assay to find their non-cytotoxic concentrations on bEnd.3 cells. The enhancement on gefitinib across the BBB was evaluated by cytotoxicity assay on human lung adenocarcinoma PC9 cells under the bEnd.3 cells grown on the transwell inserts. Our findings showed that gefitinib incorporated in SUV-G+T or SUV-RF across the bEnd.3 cells significantly reduced the viability of PC9 cells more than that of free gefitinib. Furthermore, SUV-RF showed no cytotoxicity on bEnd.3 cells and did not affect the transendothelial electrical resistance (TEER) and transendothelial permeability of sodium fluorescein across the BBB model. Moreover, flow cytometry and confocal laser scanning microscopy were employed to evaluate the endocytosis pathways of SUV-RF. The results indicated that the uptake into bEnd.3 cells was mainly through adsorptive-mediated mechanism via electrostatic interaction and partially through clathrin-mediated endocytosis. In conclusion, cell penetrating peptide-conjugated SUV-RF shed light on improving drug transport across the BBB via modulating the transcytosis pathway(s).

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Section: Discussionmentioning

confidence: 99%

“…GSH, an endogenous tripeptide, possesses a central nervous system (CNS) concentration up to 3 mM [12]. It has antioxidant-like characteristics and is readily transported across the BBB [13].…”

Section: Introductionmentioning

confidence: 99%

Enhancing Anticancer Effect of Gefitinib across the Blood–Brain Barrier Model Using Liposomes Modified with One α-Helical Cell-Penetrating Peptide or Glutathione and Tween 80

Lin¹,

Hong²,

Wang³

et al. 2016

IJMS

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show abstract

“…In‐Vitro BBB Permeation Model : A Transwell model was established to investigate the BBB permeability of the H–S–R NPs1, which was adapted from a previously reported method . Briefly, Transwell permeable supports with 0.4‐μm porous membranes (Corning Inc., NY, USA) were purchased and coated with rat tail collagen I (BD Biosciences).…”

Section: Methodsmentioning

confidence: 99%

Dual‐Targeting Heparin‐Based Nanoparticles that Re‐Assemble in Blood for Glioma Therapy through Both Anti‐Proliferation and Anti‐Angiogenesis

Wang

Yang

Zhang

et al. 2016

Adv Funct Materials

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The efficient and specific delivery of nanoparticles (NPs) to brain tumors is crucial for successful glioma treatment. Heparin‐based polymers decorated with two peptides self‐assemble into multi‐functional NPs that specifically target glioma cells. These NPs re‐self‐assemble to a smaller size in blood, which is beneficial for in‐vivo brain drug delivery. The hydrodynamic size of one type of these NPs is 63 ± 11 nm under blood‐mimic conditions (10% fetal bovine serum), but it is 164 ± 16 nm in water. Additionally their zeta potential is more neutral in the blood‐mimic conditions. Transmission electron microscopy reveals the morphology of the spherical NPs. In vitro experiments demonstrate that the NPs exhibit a high cellular uptake and the ability to efficiently discourage proliferation, endothelial‐lined vessels, and vasculogenic mimicry. In vivo studies demonstrate that the NPs can by‐pass the normal blood–brain and blood–(brain tumor) barriers and specifically accumulate in glioma tissues; moreover, they present an excellent anti‐glioma effect in subcutaneous/intracranial glioma‐bearing mice. Their superiority is due to their appropriate size in blood and the synergic effect arising from their targeting of two different receptors. The data suggests that these NPs are ideal for anti‐glioma therapy.

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“…Since there are many kinds of receptors expressed on the endothelial BBB, different studies attempted to exploit some of them to facilitate the transport of NPs. Among the most common receptors extensively studied are the glucose transporter GLUT 99-102 , transferrin receptor 33,102-105 , LDL receptor 106,107 and glutathione transporters[108][109][110] . It was also shown that dual targeting can improve the BBB passage by adding two targeting moieties: one that first target the BBB and then target specifically the glioma cells99,102,106 .…”

mentioning

confidence: 99%

Harnessing nanomedicine for therapeutic intervention in glioblastoma

Gutkin

Peer

2016

Expert Opinion on Drug Delivery

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Glioblastoma is a type of brain cancer arises from glial cells. Glioblastoma multiforme (GBM), a subtype of glioblastoma, is the most common and most aggressive primary brain tumor. Currently, GBM therapy includes surgery and post-operative high-doses of radiation and chemotherapy. This therapeutic strategy has a limited contribution in extending the survival rate of GBM patients. Areas covered: Herein, we focus on harnessing nanoscale drug delivery strategies to treat brain malignancies. Specifically, we briefly discuss the challenges facing GBM therapy such as restricted passage across the blood-brain barrier (BBB) and low enhanced permeability and retention effect. Next, we describe different pathways to address these challenges. Finally, we discuss the field of nanomedicine, which emerged as a promising platform for drug delivery to brain malignancies. Expert opinion: Countless strategies have been applied in preclinical and clinical settings to treat GBM. Among them is the use of different types of nanoparticles (NPs) and viruses with different approaches to cross or bypass the BBB. We suggest here a paradigm shift in thinking about crossing the BBB and tumor penetration as fundamental issues that need to be address in order to improve the therapeutic outcome in GBM.

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Brain-Targeted Delivery of Docetaxel by Glutathione-Coated Nanoparticles for Brain Cancer

Cited by 58 publications

References 26 publications

Enhancing Anticancer Effect of Gefitinib across the Blood–Brain Barrier Model Using Liposomes Modified with One α-Helical Cell-Penetrating Peptide or Glutathione and Tween 80

Enhancing Anticancer Effect of Gefitinib across the Blood–Brain Barrier Model Using Liposomes Modified with One α-Helical Cell-Penetrating Peptide or Glutathione and Tween 80

Dual‐Targeting Heparin‐Based Nanoparticles that Re‐Assemble in Blood for Glioma Therapy through Both Anti‐Proliferation and Anti‐Angiogenesis

Harnessing nanomedicine for therapeutic intervention in glioblastoma

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