Intranasal delivery of targeted polyfunctional gold–iron oxide nanoparticles loaded with therapeutic microRNAs for combined theranostic multimodality imaging and presensitization of glioblastoma to temozolomide

Sukumar, Uday Kumar; Bose, Rajendran J.C.; Malhotra, Meenakshi; Babikir, Husam; Afjei, Rayhaneh; Robinson, Elise; Zeng, Yitian; Chang, Edwin; Habte, Frezghi; Sinclair, Robert; Gambhir, Sanjiv S.; Massoud, Tarik F.; Paulmurugan, Ramasamy

doi:10.1016/j.biomaterials.2019.119342

Cited by 181 publications

(142 citation statements)

References 34 publications

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“…AuNPs for neuronal uptake can be utilized through two main routes: crossing the BBB and through the olfactory nerves. During an investigation, researchers successfully employed nose-to-brain direct transport pathway to deliver theranostic polyfunctional gold-iron oxide nanoparticles, surface loaded with miR-100 and antimiR-21, to GBMs in mice [85]. A study reported the formulation of resveratrol-loaded transferosomes and nanoemulsions labelled with gold nanoparticles for targeting the brain through intranasal route.…”

Section: Gold Nanoparticlesmentioning

confidence: 99%

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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Although the global prevalence of neurological disorders such as Parkinson's disease, Alzheimer's disease, glioblastoma, epilepsy, and multiple sclerosis is steadily increasing, effective delivery of drug molecules in therapeutic quantities to the central nervous system (CNS) is still lacking. The blood brain barrier (BBB) is the major obstacle for the entry of drugs into the brain, as it comprises a tight layer of endothelial cells surrounded by astrocyte foot processes that limit drugs' entry. In recent times, intranasal drug delivery has emerged as a reliable method to bypass the BBB and treat neurological diseases. The intranasal route for drug delivery to the brain with both solution and particulate formulations has been demonstrated repeatedly in preclinical models, including in human trials. The key features determining the efficacy of drug delivery via the intranasal route include delivery to the olfactory area of the nares, a longer retention time at the nasal mucosal surface, enhanced penetration of the drugs through the nasal epithelia, and reduced drug metabolism in the nasal cavity. This review describes important neurological disorders, challenges in drug delivery to the disordered CNS, and new nasal delivery techniques designed to overcome these challenges and facilitate more efficient and targeted drug delivery. The potential for treatment possibilities with intranasal transfer of drugs will increase with the development of more effective formulations and delivery devices. Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neurodegenerative disease, leading to the development of bradykinesia and tremors of cardinal motor functions ( Figure 2) [3]. PD models specifically show a decrease in dopamine transporters, which are responsible for dopamine uptake by dopaminergic neurons and progression of neuronal communications. Reduced Figure 1. Schematic demonstrating various transport systems that shuttle molecules across the BBB. Very small amount of water-soluble compounds cross through the tight junctions (paracellular), whereas lipid-soluble agents traverse via the transcellular lipophilic pathway. Selective transport systems exist for glucose, amino acids, nucleosides, and other substances, in addition to specific receptor-mediated endocytosis for certain proteins such as insulin and transferrin. (AZT = azathioprine). List of CNS Diseases Parkinson's Disease (PD)PD, occurring primarily in the substantia nigra, is the second-most common neuro...

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Section: Gold Nanoparticlesmentioning

confidence: 99%

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

et al. 2020

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“…29 To further explore the therapeutic outcomes of the combination treatment in vivo, GL261 intracranial tumor-bearing mice were treated with various formulations. In contrast to a recent study on IN administration of polyfunctional goldiron oxide nanoparticles loaded with therapeutic miRNAs to enhance apoptosis of glioma cells, 30 in the present study, for the first time, a novel non-invasive and simple technique was employed to deliver poly(I:C) in a manner that bypasses the BBB to treat glioma by inducing a local anti-tumor immune response. The treatment started from day 7 after tumor inoculation and ended on day 11.…”

Section: In Administration Of Au@pp/poly(i:c) Inhibited Intracranial mentioning

confidence: 96%

<p>Intranasal Delivery of Immunotherapeutic Nanoformulations for Treatment of Glioma Through in situ Activation of Immune Response</p>

Yin¹,

Li²,

Ke³

et al. 2020

IJN

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Purpose: Some chemotherapeutics have been shown to induce both the release of damageassociated molecular patterns (DAMPs) and the production of type I interferon (IFN-I), leading to immunogenic cell death (ICD). However, the standard chemotherapy drug for glioma, temozolomide (TMZ), cannot induce ICD as it cannot activate IFN-I signaling. Moreover, inefficient delivery of immunostimulants across the blood-brain barrier (BBB) is the main obstacle to overcome in order to induce local immune responses in the brain. Methods: A new oligonucleotide nanoformulation (Au@PP)/poly(I:C)) was constructed by coating gold nanoparticles (AuNPs) with methoxypolyethylene glycol (mPEG)-detachable (d)-polyethyleneimine (PEI) (Au@PP) followed by inducing the formation of electrostatic interactions with polyinosinic-polycytidylic acid (poly(I:C)). Intracranial GL261 tumorbearing C57BL/6 mice were used to explore the therapeutic outcomes of Au@PP/poly(I:C) plus TMZ in vivo. The anti-tumor immune response in the brain induced by this treatment was analyzed by RNA sequencing and immunohistochemical analyses. Results: Au@PP/poly(I:C) induced IFN-I production after endocytosis into glioma cells in vitro. Additionally, Au@PP/poly(I:C) was efficiently accumulated in the glioma tissue after intranasal administration, which allowed the nanoformulation to enter the brain while bypassing the BBB. Furthermore, Au@PP/poly(I:C) plus TMZ significantly improved the overall survival of the tumor-bearing mice compared with group TMZ only. RNA sequencing and immunohistochemical analyses revealed efficient immune response activation and T lymphocyte infiltration in the Au@PP/poly(I:C) plus TMZ group. Conclusion: This study demonstrates that intranasal administration of Au@PP/poly(I:C) combined with TMZ induces ICD, thereby stimulating an in situ immune response to inhibit glioma growth.

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“…Second, another method to enable anti-GBM drugs reaching GBM tumors without being stuck by the BBB, consists of injecting these drugs by an intranasal route as carried out with Polyplex coated magnetite (Nano-co-Plex) loaded with BCNU or T7-targeted polyGIONs, enabling the active principles, miRNAs or BCNU, to efficiently reach GBM tumors [23,36]. First, an intratumor administration route could be used to enable anti-GBM drugs to directly reach GBM tumors without having to cross the BBB.…”

Section: Nano-drugs Improve Gbm Drug Deliverymentioning

confidence: 99%

Nano-Therapies for Glioblastoma Treatment

Alphandéry

2020

Cancers

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Traditional anti-cancer treatments are inefficient against glioblastoma, which remains one of the deadliest and most aggressive cancers. Nano-drugs could help to improve this situation by enabling: (i) an increase of anti-glioblastoma multiforme (GBM) activity of chemo/gene therapeutic drugs, notably by an improved diffusion of these drugs through the blood brain barrier (BBB), (ii) the sensibilization of radio-resistant GBM tumor cells to radiotherapy, (iii) the removal by surgery of infiltrating GBM tumor cells, (iv) the restoration of an apoptotic mechanism of GBM cellular death, (v) the destruction of angiogenic blood vessels, (vi) the stimulation of anti-tumor immune cells, e.g., T cells, NK cells, and the neutralization of pro-tumoral immune cells, e.g., Treg cells, (vii) the local production of heat or radical oxygen species (ROS), and (viii) the controlled release/activation of anti-GBM drugs following the application of a stimulus. This review covers these different aspects.

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Intranasal delivery of targeted polyfunctional gold–iron oxide nanoparticles loaded with therapeutic microRNAs for combined theranostic multimodality imaging and presensitization of glioblastoma to temozolomide

Cited by 181 publications

References 34 publications

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

<p>Intranasal Delivery of Immunotherapeutic Nanoformulations for Treatment of Glioma Through in situ Activation of Immune Response</p>

Nano-Therapies for Glioblastoma Treatment

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