Nanoscale Materials for Tackling Brain Cancer: Recent Progress and Outlook

Rozhkova, Elena A.

doi:10.1002/adma.201004714

Cited by 55 publications

(31 citation statements)

References 151 publications

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“…Last, sustainable dosing at the tumor site is necessary, given the dynamic nature of malignant tumor genetic/epigenetic adaptations to therapy. Numerous nano constructs have been designed to address each of these elements (32,34,35,68,69); our approach comprehensively combines the favorable benefits of several modalities. It builds on the blood vessel-targeting capacity of the customizable 7C1 lipopolymeric nano vehicle, which has excellent safety profiles (14,15,23,70).…”

Section: Discussionmentioning

confidence: 99%

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression

Khan

Suvà

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

112

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Brain tumor-initiating cells (BTICs) have been identified as key contributors to therapy resistance, recurrence, and progression of diffuse gliomas, particularly glioblastoma (GBM). BTICs are elusive therapeutic targets that reside across the blood-brain barrier, underscoring the urgent need to develop novel therapeutic strategies. Additionally, intratumoral heterogeneity and adaptations to therapeutic pressure by BTICs impede the discovery of effective anti-BTIC therapies and limit the efficacy of individual gene targeting. Recent discoveries in the genetic and epigenetic determinants of BTIC tumorigenesis offer novel opportunities for RNAi-mediated targeting of BTICs. Here we show that BTIC growth arrest in vitro and in vivo is accomplished via concurrent siRNA knockdown of four transcription factors (SOX2, OLIG2, SALL2, and POU3F2) that drive the proneural BTIC phenotype delivered by multiplexed siRNA encapsulation in the lipopolymeric nanoparticle 7C1. Importantly, we demonstrate that 7C1 nano-encapsulation of multiplexed RNAi is a viable BTICtargeting strategy when delivered directly in vivo in an established mouse brain tumor. Therapeutic potential was most evident via a convection-enhanced delivery method, which shows significant extension of median survival in two patient-derived BTIC xenograft mouse models of GBM. Our study suggests that there is potential advantage in multiplexed targeting strategies for BTICs and establishes a flexible nonviral gene therapy platform with the capacity to channel multiplexed RNAi schemes to address the challenges posed by tumor heterogeneity.siRNA | lipopolymeric nanoparticle | glioblastoma transcription factor | brain tumor-initiating cells | convection-enhanced delivery G lioblastoma (GBM) is one of the most challenging tumors to treat (1, 2). Despite decades of research and maximal clinical combination therapy encompassing surgical resection, chemotherapy, and radiation, the median life expectancy of patients has not been extended beyond 2 y after diagnosis (2). Increasing evidence suggests that the genetic, epigenetic, and signaling heterogeneity of GBM underlies the ineffectiveness of currently available therapeutics (1, 2). Additionally, therapeutic schemes devised to challenge brain tumor cells are frequently thwarted by insufficient delivery caused by pharmacokinetics, the blood-brain barrier (BBB), and an altered tumor microenvironment in which tumor-derived signaling recruits immunomodulatory cells and induces extracellular matrix remodeling to build safe harbors of tumorigenic niches (3-5). These obstacles call for tailored therapeutic strategies to counter tumor heterogeneity and overcome roadblocks in delivery. RNAi targeting drivers of tumorigenesis shows strong potential to supplement the development of traditional small-molecule pharmaceutics (6). However, delivery remains a key obstacle for efficient RNAi against tumor drivers (5,7,8). RNA-sequencing analysis of patient tissue combined with histology and in situ hybridization (Ivy Glioblastoma Atlas Pro...

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Section: Discussionmentioning

confidence: 99%

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression

Khan

Suvà

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

112

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“…Figure 3 shows the FT-IR spectra of pure Cys and FePt-Cys NPs. The absorption bands at 3,200-2,900 cm -1 and ~1,580 cm -1 in Figure 3A were designated as the stretching vibrations of NH 3 + and COO -, respectively. These absorption bands were shifted to the higher wavenumbers of ~3,420 cm -1 and 1,605 cm -1 in FT-IR spectrum of FePt-Cys NPs ( Figure 3B), respectively, because of the change in the dipole moment when Cys was adsorbed on the surface of NPs with high electron density.…”

Section: Resultsmentioning

confidence: 99%

“…1 In the past decade, numerous novel strategies based on various nanomaterials have been developed to conquer the highly mortal brain tumors. [2][3][4][5] Interesting topics in this field include the targeted and controlled delivery system of anticancer drugs; [6][7][8][9] photodynamic, photothermal, and magnetothermal therapy of tumors; [10][11][12][13][14][15][16] and MRI, CT, and fluorescent imaging of brain tumors. [17][18][19][20][21][22] Among various nanomaterials, magnetic nanoparticles (NPs) such as superparamagnetic iron oxide NPs (SPIONs) are the most extensively studied.…”

Section: Introductionmentioning

confidence: 99%

Water-soluble l-cysteine-coated FePt nanoparticles as dual MRI/CT imaging contrast agent for glioma

Liang¹,

Zhou²,

Wang³

et al. 2015

IJN

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Nanoparticles (NPs) are advantageous for the delivery of diagnosis agents to brain tumors. In this study, we attempted to develop an l -cysteine coated FePt (FePt-Cys) NP as MRI/CT imaging contrast agent for the diagnosis of malignant gliomas. FePt-Cys NPs were synthesized through a co-reduction route, which was characterized by transmission electron microscopy, high-resolution transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared spectroscopy, and dynamic light scattering. The MRI and CT imaging ability of FePt-Cys NPs was evaluated using different gliomas cells (C6, SGH44, U251) as the model. Furthermore, the biocompatibility of the as-synthesized FePt-Cys NPs was evaluated using three different cell lines (ECV304, L929, and HEK293) as the model. The results showed that FePt-Cys NPs displayed excellent biocompatibility and good MRI/CT imaging ability, thereby indicating promising potential as a dual MRI/CT contrast agent for the diagnosis of brain malignant gliomas.

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“…Nanocarriers when delivered by CED show an increased distribution volume and a longer therapeutic retention within the tumor mass. [1a,3] Significant efforts have been made toward the application of nanocarrier delivery of small-molecule drugs by CED. [3a–c] However, the efflux proteins highly expressed on the BBB efficiently pump chemodrugs out of the central nervous system, decreasing the effectiveness of such treatments.…”

mentioning

confidence: 99%

“…[1a,3] Significant efforts have been made toward the application of nanocarrier delivery of small-molecule drugs by CED. [3a–c] However, the efflux proteins highly expressed on the BBB efficiently pump chemodrugs out of the central nervous system, decreasing the effectiveness of such treatments. [1a] CED infusion of protein toxins has been previously used for GBM treatment but has been associated with significant toxicity toward normal brain tissue as well as systemic toxicity and has yet to show an increased survival benefit in clinical trials.…”

mentioning

confidence: 99%

Tunable Lipidoid‐Telodendrimer Hybrid Nanoparticles for Intracellular Protein Delivery in Brain Tumor Treatment

Wang

Bodman

Shi

et al. 2016

Small

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A strategy to precisely engineer lipidoid‐telodendrimer binary hybrid nanoparticles that offer enhanced cell membrane permeability for therapeutic proteins to reach the intracellular targets is established. The highly controllable biochemical and physical properties of the nanoparticles make them promising for protein‐based brain cancer treatment with the assistance of convection‐enhanced delivery.

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Nanoscale Materials for Tackling Brain Cancer: Recent Progress and Outlook

Cited by 55 publications

References 151 publications

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression

Multiplexed RNAi therapy against brain tumor-initiating cells via lipopolymeric nanoparticle infusion delays glioblastoma progression

Water-soluble l-cysteine-coated FePt nanoparticles as dual MRI/CT imaging contrast agent for glioma

Tunable Lipidoid‐Telodendrimer Hybrid Nanoparticles for Intracellular Protein Delivery in Brain Tumor Treatment

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