Nanocarriers for the treatment of glioblastoma multiforme: Current state-of-the-art

Karim, Rezaul; Palazzo, Clémence; Évrard, Brigitte; Piel, Géraldine

doi:10.1016/j.jconrel.2016.02.026

Cited by 201 publications

(128 citation statements)

References 190 publications

Supporting

Mentioning

123

Contrasting

Unclassified

Order By: Relevance

“…One method could be the use of nanoparticles [37][38][39]. For instance, Gao and colleagues showed an increased IL-13 peptide uptake by glioma if the cytokine was coupled to nanoparticles [40].…”

Section: Discussionmentioning

confidence: 99%

Targeting the Potassium Channel Kv1.3 Kills Glioblastoma Cells

et al. 2017

View full text Add to dashboard Cite

Background/Aims: Glioblastoma (GBM) is one of the most aggressive cancers, counting for a high number of the newly diagnosed patients with central nervous system (CNS) cancers in the United States and Europe. Major features of GBM include aggressive and invasive growth as well as a high resistance to treatment. Kv1.3, a potassium channel of the shaker family, is expressed in the inner mitochondrial membrane of many cancer cells. Inhibition of mitochondrial Kv1.3 was shown to induce apoptosis in several tumor cells at doses that were not lethal for normal cells. Methods: We investigated the expression of Kv1.3 in different glioma cell lines by immunocytochemistry, western blotting and electron microscopy and analyzed the effect of newly synthesized, mitochondria-targeted, Kv1.3 inhibitors on the induction of cell death in these cells. Finally, we performed in vivo studies on glioma bearing mice. Results: Here, we report that Kv1.3 is expressed in mitochondria of human and murine GL261, A172 and LN308 glioma cells. Treatment with the novel Kv1.3 inhibitors PAPTP or PCARBTP as well as with clofazimine induced massive cell death in glioma cells, while Psora-4 and PAP-1 were almost without effect. However, in vivo experiments revealed that the drugs had no effect on orthotopic brain tumors in vivo. Conclusion: These data serve as proof of principle that Kv1.3 inhibitors kills GBM cells, but drugs that act in vivo against glioblastoma must be developed to translate these findings in vivo.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting the Potassium Channel Kv1.3 Kills Glioblastoma Cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…[1] They are being used in a variety of applications, from the biomedical [2][3][4] to the agricultural fields. [5][6][7] Nanocarriers are used to deliver payloads and can target specific cells and organs, [8] while improving the bioavailability, stability, [9] and efficiency of the payloads.…”

Section: Introductionmentioning

confidence: 99%

Large‐Scale Preparation of Polymer Nanocarriers by High‐Pressure Microfluidization

Alkanawati

Wurm

Thérien-Aubin

et al. 2017

Macro Materials & Eng

View full text Add to dashboard Cite

by dispersion, suspension emulsion, or miniemulsion polymerization, while the preparation of polymer nanocarriers made from preformed polymers usually occurs by coacervation methods such as salting out, [13] emulsification-diffusion, [14] nanoprecipitation, and supercritical fluid technology. [15,16] Among those different preparation techniques, miniemulsion is particularly attractive due to its ability to prepare nanocarriers from either mono mer or polymer while allowing for the efficient loading of large doses of therapeutic agents, which can be lipophilic and/or hydrophilic compounds. [17] Furthermore, miniemulsion provides the opportunity to finely tune particle size distribution while preparing emulsion with high solid content of polymers. [18][19][20] The crosslinking of polymer-containing nanodroplets formed by miniemulsion is a particularly attractive method to produce nanocarriers (Figure 1). Hollow nanocapsules can be prepared by a polyaddition or polycondensation reaction occurring at the droplets interface. [21] In order to prepare nanocarriers, the polymer is dissolved in a good solvent and emulsified with an immiscible nonsolvent forming the continuous phase. After the emulsification, a crosslinking agent, soluble in the continuous phase, is added to the emulsion and the poly addition or polycondensation reaction between the polymer and crosslinking agent occurs at the surface of the droplet. When the reaction kinetic is fast enough, a shell insoluble in both phases can be formed at the interface. [22] To control the size and size distribution of the nanocapsules prepared by the polyaddition/polycondensation reaction at the droplet interface, it is critical to control the preparation of the miniemulsion used as a precursor. The two main factors leading to the broadening of the size distribution of the nanodroplets during miniemulsion are (i) Ostwald ripening and (ii) coalescence of the droplets occurring through collision. The coalescence could be controlled by the addition of an appropriate surfactant, which provides electrostatic or steric stabilization thus preventing droplet coalescence. Ostwald ripening is affected by multiple factors such as droplet size, Laplace pressure, polydispersity, and solubility of the dispersed phase in the continuous phase. In general, Ostwald ripening could be limited by the addition of compounds increasing the osmotic pressure in the system. These chemicals need to be highly insoluble in the continuous phase but completely soluble in the Nanocapsules Polymer nanocarriers are used as transport modules in the design of the next generation of drug delivery technology. However, the applicability of nanocarrier-based technology depends strongly on our ability to precisely control and reproduce their synthesis on a large scale because their properties and performances are strongly dependent on their size and shape. Fundamental studies and practical applications of polymer nanocarriers are hampered by the difficulty of using the current methods to produce monodispersed ...

show abstract

“…In the current scenario, this approach must be directed toward surpassing acquired resistance to conventional chemotherapy and implementing strategies to boost the distribution across the brain endothelium in the case of systemic administration [16].…”

Section: The Nanomedicine Approachmentioning

confidence: 99%

Managing CNS Tumors: The Nanomedicine Approach

Aparicio-Blanco¹,

Torres-Suárez²

2017

New Approaches to the Management of Primary and Secondary CNS Tumors

View full text Add to dashboard Cite

Albeit the rapidly evolving knowledge about tumor biochemistry enables various new drug molecules to be designed as treatments, malignant central nervous system (CNS) tumors remain untreatable due to the failure to expose the entire tumor to such therapeutics at pharmacologically meaningful quantities. Therefore, drug delivery in CNS tumors must be properly addressed, as otherwise, novel therapies will continue to fail. In this regard, nanomedicine poses an appealing platform for efficient drug delivery to the CNS, since it may be targeted to improve the drug availability in the site of action, which would be translated into lower drug doses and fewer side effects. Hence, the accumulation of data about the CNS physiology and their relevant receptors, the widening therapeutic armamentarium of drugs potentially useful in CNS chemotherapy and the alternative routes for administration may envisage nanomedicines as a forthcoming routine approach. Indeed, on the basis of the promising results gathered from preclinical studies of nanomedicine-based therapy both systemically and locally administered, some nanomedicines have already been approved for clinical trials in a variety of CNS tumor conditions to serve as the first steps in the translation of nanotherapy to clinic. Their outcome will steer research directions for further improvements.

show abstract

Nanocarriers for the treatment of glioblastoma multiforme: Current state-of-the-art

Cited by 201 publications

References 190 publications

Targeting the Potassium Channel Kv1.3 Kills Glioblastoma Cells

Targeting the Potassium Channel Kv1.3 Kills Glioblastoma Cells

Large‐Scale Preparation of Polymer Nanocarriers by High‐Pressure Microfluidization

Managing CNS Tumors: The Nanomedicine Approach

Contact Info

Product

Resources

About