Targeted delivery of nano-PTX to the brain tumor-associated macrophages

Zou, Lei; Tao, Youhua; Payne, Gregory F.; Do, Linh; Thomas, Tima; Rodríguez, Juan C.; Dou, Haoran

doi:10.18632/oncotarget.14169

Cited by 37 publications

(17 citation statements)

References 59 publications

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“…43,49,105 On the other hand, RVG is a neurotropic virus peptide that binds to the nicotinic acetylcholine receptors and facilitates nanoparticle delivery to the brain and brain tumors. 47,[53][54][55]60 When evaluating nanoparticles' capacity to internalize GBM cells and inhibit the expression of miR-92b in vitro, we observed that SNAs, SNA-Liposomes, SNA-Liposome-ApoE, and SNA-Liposome-RVG had similar delivery efficiencies than the lipofectamine used as a positive control. Our in vivo results confirmed our hypothesis that ApoE and RVG peptides would enable RNAi systemic delivery into brain tumor cells.…”

Section: Discussionmentioning

confidence: 98%

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<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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Section: Discussionmentioning

confidence: 98%

“…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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“…They showed the decreased tumor size and increased survival of mice treated with these NPs. Zou et al investigated the effectiveness of paclitaxel-loaded PLGA NPs in targeting brain tumor-associated macrophages [124]. Their results demonstrated the beneficial effects of these NPs in the treatment of gliomas.…”

Section: Plgamentioning

confidence: 99%

Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics

et al. 2020

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The blood–brain barrier (BBB) acts as a barrier to prevent the central nervous system (CNS) from damage by substances that originate from the blood circulation. The BBB limits drug penetration into the brain and is one of the major clinical obstacles to the treatment of CNS diseases. Nanotechnology-based delivery systems have been tested for overcoming this barrier and releasing related drugs into the brain matrix. In this review, nanoparticles (NPs) from simple to developed delivery systems are discussed for the delivery of a drug to the brain. This review particularly focuses on polymeric nanomaterials that have been used for CNS treatment. Polymeric NPs such as polylactide (PLA), poly (D, L-lactide-co-glycolide) (PLGA), poly (ε-caprolactone) (PCL), poly (alkyl cyanoacrylate) (PACA), human serum albumin (HSA), gelatin, and chitosan are discussed in detail.

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“…Receptor-mediated transcytosis offers a highly specific transport mechanism through the binding of conjugated ligands to specific receptors. With respect to CNS macrophage targeting, lactoferrin [222], transferrin receptor binding peptide [224], rabies virus glycoprotein [225], and mannose [197] are among those that have been explored.…”

Section: Optimising Delivery and Np/mp Uptake In Macrophagesmentioning

confidence: 99%

Nanomodulation of Macrophages in Multiple Sclerosis

Nally

Santi

McCoy

2019

Cells

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Multiple Sclerosis (MS) is a chronic demyelinating autoimmune disease primarily affecting young adults. Despite an unclear causal factor, symptoms and pathology arise from the infiltration of peripheral immune cells across the blood brain barrier. Accounting for the largest fraction of this infiltrate, macrophages are functionally heterogeneous innate immune cells capable of adopting either a pro or an anti-inflammatory phenotype, a phenomenon dependent upon cytokine milieu in the CNS. This functional plasticity is of key relevance in MS, where the pro-inflammatory state dominates the early stage, instructing demyelination and axonal loss while the later anti-inflammatory state holds a key role in promoting tissue repair and regeneration in later remission. This review highlights a potential therapeutic benefit of modulating macrophage polarisation to harness the anti-inflammatory and reparative state in MS. Here, we outline the role of macrophages in MS and look at the role of current FDA approved therapeutics in macrophage polarisation. Moreover, we explore the potential of particulate carriers as a novel strategy to manipulate polarisation states in macrophages, whilst examining how optimising macrophage uptake via nanoparticle size and functionalisation could offer a novel therapeutic approach for MS.

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Targeted delivery of nano-PTX to the brain tumor-associated macrophages

Cited by 37 publications

References 59 publications

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

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

Multifunctional Polymeric Nanoplatforms for Brain Diseases Diagnosis, Therapy and Theranostics

Nanomodulation of Macrophages in Multiple Sclerosis

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