Mechanisms of enhanced antiglioma efficacy of polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles by focused ultrasound

Li, Yingjia; Wu, Manxiang; Zhang, Nisi; Tang, Caiyun; Jiang, Peng; Liu, Xin; Yan, Fei; Zheng, Hairong

doi:10.1111/jcmm.13695

Cited by 40 publications

(23 citation statements)

References 45 publications

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“…26 In this study, the FePt nanoparticles were incorporated into phospholipid micelles (SM80s), which were tailored to minimize interaction with the reticuloendothelial system in order to extend their lifetime in the blood and to avoid the buildup of a protein corona by means of their polyethyleneglycolcoated surfaces. The addition of a polysorbate-80 [46][47][48][49][50] coating and ApoE2 50 provided a mechanism by which the nanoparticles were transported through the BBB via interaction with the LDL receptors in the brain. To specifically reveal neuroinflammation, the SM80s were targeted to activated microglia/macrophages by conjugating anti-Iba-1 antibodies.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal monitoring of microglial/macrophage activation in ischemic rat brain using Iba-1-specific nanoparticle-enhanced magnetic resonance imaging

Sillerud

Yang

et al. 2020

J Cereb Blood Flow Metab

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Microglial/macrophage activation plays a dual role in response to brain injury after a stroke, promoting early neuroinflammation and benefit for neurovascular recovery. Therefore, the dynamics of stroke-induced cerebral microglial/macrophage activation are of substantial interest. This study used novel anti-Iba-1-targeted superparamagnetic iron–platinum (FePt) nanoparticles in conjunction with magnetic resonance imaging (MRI) to measure the spatiotemporal changes of the microglial/macrophage activation in living rat brain for four weeks post-stroke. Ischemic lesion areas were identified and measured using T2-weighted MR images. After injection of the FePt-nanoparticles, T2*-weighted MR images showed that the nanoparticles were seen solely in brain regions that coincided with areas of active microglia/macrophages detected by post-mortem immunohistochemistry. Good agreement in morphological and distributive dynamic changes was also observed between the Fe+-cells and the Iba-1+-microglia/macrophages. The spatiotemporal changes of nanoparticle detected by T2*-weighted images paralleled the changes of microglial/macrophage activation and phenotypes measured by post-mortem immunohistochemistry over the four weeks post-stroke. Maximum microglial/macrophage activation occurred seven days post-stroke for both measures, and the diminished activation found after two weeks continued to four weeks. Our results suggest that nanoparticle-enhanced MRI may constitute a novel approach for monitoring the dynamic development of neuroinflammation in living animals during the progression and treatment of stroke.

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Section: Discussionmentioning

confidence: 99%

Longitudinal monitoring of microglial/macrophage activation in ischemic rat brain using Iba-1-specific nanoparticle-enhanced magnetic resonance imaging

Sillerud

Yang

et al. 2020

J Cereb Blood Flow Metab

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“…This study used polysorbate-80-stabilized poly (D,L-lactide-co-glycolate) (PLGA) polymeric nanoparticles loaded with paclitaxel paired with FUS in mouse models of glioma. They found that using PLGA nanoparticles and FUS in combination to deliver paclitaxel across the BBB disrupted endothelial cell tight junctions, decreased P-glycoprotein expression, and allowed for greater antitumor efficacy of the paclitaxel ( 52 ). Liposomes, like polymeric nanoparticles, can also encapsulate drugs.…”

Section: Approaches To Mitigate the Bbb For Drug Deliverymentioning

confidence: 99%

Developments in Blood-Brain Barrier Penetrance and Drug Repurposing for Improved Treatment of Glioblastoma

et al. 2018

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Glioblastoma (GBM) is one of the most common, deadly, and difficult-to-treat adult brain tumors. Surgical removal of the tumor, followed by radiotherapy (RT) and temozolomide (TMZ) administration, is the current treatment modality, but this regimen only modestly improves overall patient survival. Invasion of cells into the surrounding healthy brain tissue prevents complete surgical resection and complicates treatment strategies with the goal of preserving neurological function. Despite significant efforts to increase our understanding of GBM, there have been relatively few therapeutic advances since 2005 and even fewer treatments designed to effectively treat recurrent tumors that are resistant to therapy. Thus, while there is a pressing need to move new treatments into the clinic, emerging evidence suggests that key features unique to GBM location and biology, the blood-brain barrier (BBB) and intratumoral molecular heterogeneity, respectively, stand as critical unresolved hurdles to effective therapy. Notably, genomic analyses of GBM tissues has led to the identification of numerous gene alterations that govern cell growth, invasion and survival signaling pathways; however, the drugs that show pre-clinical potential against signaling pathways mediated by these gene alterations cannot achieve effective concentrations at the tumor site. As a result, identifying BBB-penetrating drugs and utilizing new and safer methods to enhance drug delivery past the BBB has become an area of intensive research. Repurposing and combining FDA-approved drugs with evidence of penetration into the central nervous system (CNS) has also seen new interest for the treatment of both primary and recurrent GBM. In this review, we discuss emerging methods to strategically enhance drug delivery to GBM and repurpose currently-approved and previously-studied drugs using rational combination strategies.

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“…Moreover, both peptides have proven to facilitate the delivery of different nanoparticles into GBM cells in vitro and in vivo. 54,[56][57][58][59][60] In this study, we synthesized nanoparticles capable of delivering OMIs inside GBM cells in vitro and in vivo. We generated SNAs by chemically functionalizing OMIs to AuNPs.…”

Section: Introductionmentioning

confidence: 99%

<p>Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma</p>

Grafals‐Ruiz

Ríos-Vicil

Lozada-Delgado

et al. 2020

IJN

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Introduction: Glioblastoma (GBM) is the most common and lethal of the central nervous system (CNS) malignancies. The initiation, progression, and infiltration ability of GBMs are attributed in part to the dysregulation of microRNAs (miRNAs). Thus, targeting dysregulated miRNAs with RNA oligonucleotides (RNA interference, RNAi) has been proposed for GBM treatment. Despite promising results in the laboratory, RNA oligonucleotides have clinical limitations that include poor RNA stability and off-target effects. RNAi therapies against GBM confront an additional obstacle, as they need to cross the blood-brain barrier (BBB). Methods: Here, we developed gold-liposome nanoparticles conjugated with the brain targeting peptides apolipoprotein E (ApoE) and rabies virus glycoprotein (RVG). First, we functionalized gold nanoparticles with oligonucleotide miRNA inhibitors (OMIs), creating spherical nucleic acids (SNAs). Next, we encapsulated SNAs into ApoE, or RVG-conjugated liposomes, to obtain SNA-Liposome-ApoE and SNA-Liposome-RVG, respectively. We characterized each nanoparticle in terms of their size, charge, encapsulation efficiency, and delivery efficiency into U87 GBM cells in vitro. Then, they were administered intravenously (iv) in GBM syngeneic mice to evaluate their delivery efficiency to brain tumor tissue. Results: SNA-Liposomes of about 30-50 nm in diameter internalized U87 GBM cells and inhibited the expression of miRNA-92b, an aberrantly overexpressed miRNA in GBM cell lines and GBM tumors. Conjugating SNA-Liposomes with ApoE or RVG peptides increased their systemic delivery to the brain tumors of GBM syngeneic mice. SNA-Liposome-ApoE demonstrated to accumulate at higher extension in brain tumor tissues, when compared with non-treated controls, SNA-Liposomes, or SNA-Liposome-RVG. Discussion: SNA-Liposome-ApoE has the potential to advance the translation of miRNAbased therapies for GBM as well as other CNS disorders.

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Mechanisms of enhanced antiglioma efficacy of polysorbate 80‐modified paclitaxel‐loaded PLGA nanoparticles by focused ultrasound

Cited by 40 publications

References 45 publications

Longitudinal monitoring of microglial/macrophage activation in ischemic rat brain using Iba-1-specific nanoparticle-enhanced magnetic resonance imaging

Longitudinal monitoring of microglial/macrophage activation in ischemic rat brain using Iba-1-specific nanoparticle-enhanced magnetic resonance imaging

Developments in Blood-Brain Barrier Penetrance and Drug Repurposing for Improved Treatment of Glioblastoma

<p>Brain Targeted Gold Liposomes Improve RNAi Delivery for Glioblastoma</p>

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