Platinum (IV) coiled coil nanotubes selectively kill human glioblastoma cells

Thanasupawat, Thatchawan; Bergen, Hugo; Hombach‐Klonisch, Sabine; Krcek, Jerry; Ghavami, Saeid; Bigio, Marc R. Del; Krawitz, Sherry; Stelmack, Gerald L.; Halayko, Andrew J.; McDougall, Matthew; Meier, Markus; Stetefeld, Jörg; Klonisch, Thomas

doi:10.1016/j.nano.2015.01.014

Cited by 18 publications

(22 citation statements)

References 45 publications

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“…Cells were then labeled with primary antibodies Tuj 1:1,000 (Sigma T8660) 56 , DARPP32 1:400 (Cell Signaling 19A3) 55 , Ki-67 1:400 (EMD MAB4190MI) 57 , GFAP 1:1,000 (DAKO Z0334) 58,59 , Map2ab 1:500 (Sigma M1406) 60 , myosin 1:20 (Developmental Studies Hybridoma Bank D7F2) 61 , Iba1 1:500 (Wako 019-19741) 62 , Sox17 1:500 (R&D AF1924) 63 , FoxA2 1:500 (Abnova H00003170-M01) 64 , O4 1:50 (StemCell 01416) 65 , nestin (EMD Millipore ABD69, 1:5,000) 66 , DCX (Aves Labs DCX, 1:1,000) 67 or PDGFR 1:500 (Santa Cruz SC-338) 68 for 60 min at room temperature or overnight at 4 °C, and then with the appropriate fluorescently tagged secondary antibodies (1:500; Life Technologies A-21202, A-31571, A-11005, A-21206, A-21207, A-31573) for 60 min at room temperature. Hoechst dye was used to label nuclei.…”

Section: Methodsmentioning

confidence: 99%

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice

Lim¹,

Salazar²,

Wilton³

et al. 2017

Nat Neurosci

190

172

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Neural cultures derived from Huntington’s disease (HD) patient-derived induced pluripotent stem cells were used for ‘omics’ analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation. We observed a strong correlation between HD-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysregulated pathways, led to amelioration of expanded polyglutamine repeat-associated phenotypes in neural cells and of cognitive impairment and synaptic pathology in HD model R6/2 mice. These data suggest that mutant huntingtin impairs neurodevelopmental pathways that could disrupt synaptic homeostasis and increase vulnerability to the pathologic consequence of expanded polyglutamine repeats over time.

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Section: Methodsmentioning

confidence: 99%

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice

Lim¹,

Salazar²,

Wilton³

et al. 2017

Nat Neurosci

190

172

View full text Add to dashboard Cite

show abstract

“…8226/d0x40, RPMI 8226/S, and MDA 231 cells [70]. In a most recent study of RHCC associating with platinum (IV) based cisplatin, the chemotherapeutic efficacy and selectivity toward human glioblastoma cells was improved by lowering the concentration of platinum (IV) prodrug 20-fold than platinum (IV) alone [84]. …”

Section: Small Molecule Therapeuticsmentioning

confidence: 99%

Protein based therapeutic delivery agents: Contemporary developments and challenges

2017

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As unique biopolymers, proteins can be employed for therapeutic delivery. They bear important features such as bioavailability, biocompatibility, and biodegradability with low toxicity serving as a platform for delivery of various small molecule therapeutics, gene therapies, protein biologics and cells. Depending on size and characteristic of the therapeutic, a variety of natural and engineered proteins or peptides have been developed. This, coupled to recent advances in synthetic and chemical biology, has led to the creation of tailor-made protein materials for delivery. This review highlights strategies employing proteins to facilitate the delivery of therapeutic matter, addressing the challenges for small molecule, gene, protein and cell transport.

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“…Both RHCC and the acquired CP‐RHCC complex could be internalized by various cancer cell lines, but the CP‐RHCC complex showed elevated in vitro cytotoxic effects on multiple tested cell lines in comparison with CP alone, while RHCC exhibited no effect on cells . Thanasupawat et al recently utilized RHCC as a platinum ( IV ) prodrug delivery platform for glioblastoma treatment (Figure ) . The Pt( IV )‐ RHCC complex showed improved chemotherapeutic efficacy and selectivity toward human glioblastoma cells at up to 20‐fold lower concentration of Pt( IV ), as compared to Pt( IV ) prodrug alone.…”

Section: Coiled‐coil Peptide Self‐assembly As Drug Delivery Systemsmentioning

confidence: 99%

“…Side view of the RHCC protein tetramer containing Pt(IV) prodrug, where the RHCC protein is shown by van der Waals spheres and ribbon representation, with different colors for each helical chain, and the Pt(IV) prodrugs are represented by red spheres. (Reprinted with permission from Ref . Copyright 2015 Elsevier)…”

Section: Coiled‐coil Peptide Self‐assembly As Drug Delivery Systemsmentioning

confidence: 99%

α‐Helical coiled‐coil peptide materials for biomedical applications

Collier

2016

WIREs Nanomed Nanobiotechnol

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Self-assembling coiled coils, which occur commonly in native proteins, have received significant interest for the design of new biomaterials-based medical therapies. Considerable effort over recent years has led to a detailed understanding of the self-assembly process of coiled coils, and a diverse collection of strategies have been developed for designing functional materials using this motif. The ability to engineer the interface between coiled coils allows one to achieve variously connected components, leading to precisely defined structures such as nanofibers, nanotubes, nanoparticles, networks, gels, and combinations of these. Currently these materials are being developed for a range of biotechnological and medical applications, including drug delivery systems for controlled release, targeted nanomaterials, “drug-free” therapeutics, vaccine delivery systems, and others.

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Platinum (IV) coiled coil nanotubes selectively kill human glioblastoma cells

Cited by 18 publications

References 45 publications

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice

Protein based therapeutic delivery agents: Contemporary developments and challenges

α‐Helical coiled‐coil peptide materials for biomedical applications

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