Delivery of drugs into brain tumors using multicomponent silica nanoparticles

Turan, Oguz; Bielecki, Peter; Perera, Vindya S.; Lorkowski, Morgan; Covarrubias, Gil; Tong, Kathleen; Yun, Aaron; Rahmy, Abdelrahman; Ouyang, Tu; Raghunathan, Shruti; Gopalakrishnan, Ramamurthy; Griswold, Mark A.; Ghaghada, Ketan B.; Peiris, Pubudu M.; Karathanasis, Efstathios

doi:10.1039/c9nr02876e

Cited by 42 publications

(51 citation statements)

References 31 publications

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“…The synthesis of the Fe@MSN nanoparticles followed previously established methods . Briefly, the iron oxide cores were synthesized using the coprecipitation method followed by coating with citric acid.…”

Section: Resultsmentioning

confidence: 99%

“…To address the issues of today's systemically administered therapies to overcome the BBB, we have developed a multicomponent silica nanoparticle ( Figure a) . The multicomponent nanoparticle consists of a mesoporous silica shell and an iron oxide core (Fe@MSN).…”

Section: Introductionmentioning

confidence: 99%

“…Drug release from the nanoparticle can be triggered by an external low‐power radiofrequency (RF) field (Figure b). Previous work demonstrated the capabilities of the nanoparticle to deliver a chemotherapeutic drug to GBM . Rather than targeting brain tumor cells in the tumor interstitial space, we directed the nanoparticle to the remodeled vascular and near‐perivascular areas of GBM by targeting fibronectin, which is overexpressed in the near‐perivascular extracellular space of GBMs .…”

Section: Introductionmentioning

confidence: 99%

“…Previous work demonstrated the capabilities of the nanoparticle to deliver a chemotherapeutic drug to GBM . Rather than targeting brain tumor cells in the tumor interstitial space, we directed the nanoparticle to the remodeled vascular and near‐perivascular areas of GBM by targeting fibronectin, which is overexpressed in the near‐perivascular extracellular space of GBMs . Fibronectin‐targeting led to significant deposition of the nanoparticles in the perivascular areas of GBM including hypoxic regions, producing well‐distributed reservoirs of drug throughout the tumor volume.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Glioblastoma Using Multicomponent Silica Nanoparticles

Turan

Bielecki

Perera

et al. 2019

Advanced Therapeutics

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Glioblastoma multiforme (GBM) remains highly lethal. This partially stems from the presence of brain tumor initiating cells (BTICs), a highly plastic cellular subpopulation that is resistant to current therapies. In addition to resistance, the blood-brain barrier limits the penetration of most drugs into GBMs. To effectively deliver a BTIC-specific inhibitor to brain tumors, a multicomponent nanoparticle, termed Fe@MSN, which contains a mesoporous silica shell and an iron oxide core, is developed. Fibronectin-targeting ligands direct the nanoparticle to the near-perivascular areas of GBM. After Fe@MSN particles are deposited in the tumor, an external low-power radiofrequency (RF) field triggers rapid drug release due to mechanical tumbling of the particle resulting in penetration of high amounts of drug across the blood-brain tumor interface and widespread drug delivery into the GBM. The nanoparticle is loaded with the drug 1400W, which is a potent inhibitor of the inducible nitric oxide synthase (iNOS). It is shown that iNOS is preferentially expressed in BTICs and is required for their maintenance. Using the 1400W-loaded Fe@MSN and RF-triggered release, in vivo studies indicate that the treatment disrupts the BTIC population in hypoxic niches, suppresses tumor growth and significantly increases survival in BTIC-derived GBM xenografts.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Treatment of Glioblastoma Using Multicomponent Silica Nanoparticles

Turan

Bielecki

Perera

et al. 2019

Advanced Therapeutics

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“…Turan et al combined silica NPs with an iron oxide core as a treatment for a brain tumor. This inorganic-combination nanosystem allowed for the triggered drug release, by an innovative switchable mechanism, which can be activated by external radiofrequency fields near a brain tumor site [27].…”

Section: Inorganic Nanosystemsmentioning

confidence: 99%

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

et al. 2020

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Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside.

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Stimuli‐Responsive Iron Oxide Nanotheranostics: A Versatile and Powerful Approach for Cancer Therapy

Lorkowski

Atukorale

Ghaghada

et al. 2020

Adv Healthcare Materials

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Recent advancements in unravelling elements of cancer biology involved in disease progression and treatment resistance have highlighted the need for a holistic approach to effectively tackle cancer. Stimuli‐responsive nanotheranostics based on iron oxide nanoparticles are an emerging class of versatile nanomedicines with powerful capabilities to “seek, sense, and attack” multiple components of solid tumors. In this work, the rationale for using iron oxide nanoparticles and the basic physical principles that impact their function in biomedical applications are reviewed. Subsequently, recent advances in the integration of iron oxide nanoparticles with various stimulus mechanisms to facilitate the development of stimuli‐responsive nanotheranostics for application in cancer therapy are summarized. The integration of an iron oxide core with various surface coating mechanisms results in the generation of hybrid nanoconstructs with capabilities to codeliver a wide variety of highly potent anticancer therapeutics and immune modulators. Finally, emerging future directions and considerations for their clinical translation are touched upon.

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Delivery of drugs into brain tumors using multicomponent silica nanoparticles

Abstract: After targeting the nanoparticle to brain tumors, widespread drug delivery to the entire tumor is triggered by a radiofrequency field.

Cited by 42 publications

References 31 publications

Treatment of Glioblastoma Using Multicomponent Silica Nanoparticles

Treatment of Glioblastoma Using Multicomponent Silica Nanoparticles

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

Stimuli‐Responsive Iron Oxide Nanotheranostics: A Versatile and Powerful Approach for Cancer Therapy

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