Trivalent galactosyl-functionalized mesoporous silica nanoparticles as a target-specific delivery system for boron neutron capture therapy

Lai, Chian-Hui; Lai, Nien-Chu; Chuang, Yung-Jen; Chou, Fong‐In; Yang, Chun-Chuan; Lin, Chun‐Cheng

doi:10.1039/c3nr02594b

Cited by 40 publications

(31 citation statements)

References 50 publications

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“…Furthermore, because the track of a particles generated by boron-neutron capture is 10 µm at most, it is necessary that a sufficient proportion of 10 B penetrate inside cells for optimal efficiency. Large amounts of boron might be loaded into nanoparticle mesopores as o-carborane [30], however there is a risk of carborane leakage and unpredictable boron distribution. Here, we propose to attach 10 [31,32].…”

Section: Resultsmentioning

confidence: 99%

Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers

Varès

Jallet²,

Matsumoto

et al. 2018

Preprint

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AbstractTreatment resistance, relapse and metastasis remain critical issues in some challenging cancers, such as chondrosarcomas. Boron-neutron Capture Therapy (BNCT) is a targeted radiation therapy modality that relies on the ability of boron atoms to capture low energy neutrons, yielding high linear energy transfer alpha particles. We have developed an innovative boron-delivery system for BNCT, composed of multifunctional fluorescent mesoporous silica nanoparticles (B-MSNs), grafted with an activatable cell penetrating peptide (ACPP) for improved penetration in tumors and with Gadolinium for magnetic resonance imaging (MRI) in vivo. Chondrosarcoma cells were exposed in vitro to an epithermal neutron beam after B-MSNs administration. BNCT beam exposure successfully induced DNA damage and cell death, including in radio-resistant ALDH+ cancer stem cells (CSCs), suggesting that BNCT using this system might be a suitable treatment modality for chondrosarcoma or other hard-to-treat cancers.

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Section: Resultsmentioning

confidence: 99%

Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers

Varès

Jallet²,

Matsumoto

et al. 2018

Preprint

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“…A targeted multi-functional mesoporous silica nanoparticle, conjugated with trivalent galactosyl ligands and filled with carborane, was endocytosed by cells and released from lysosomes into the cellular cytoplasm. Further, compared with BSH, these nanoparticles provided a higher efficiency of delivery of boron atoms and a better effect of BNCT in neutron irradiation experiments [21]. High boron content and significant antitumor effect after thermal neutron irradiation were observed in mice injected with BSH-encapsulating 10% distearoyl boron lipid liposomes at a dose of 15 mg B/kg [22].…”

Section: Discussionmentioning

confidence: 99%

Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy

Sun

Huang

et al. 2016

Oncotarget

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The uptake of (10)boron by tumor cells plays an important role for cell damage in boron neutron capture therapy (BNCT). CD133 is frequently expressed in the membrane of glioma stem cells (GSCs), resistant to radiotherapy and chemotherapy, and represents a potential therapeutic target. To increase (10)boron uptake in GSCs, we created a polyamido amine dendrimer, conjugated CD133 monoclonal antibodies, encapsulating mercaptoundecahydrododecaborate (BSH) in void spaces, and monitored the uptake of the bioconjugate nanoparticles by GSCs in vitro and in vivo. Fluorescence microscopy showed the specific uptake of the bioconjugate nanoparticles by CD133-positive GSCs. Treatment with the biconjugate nanoparticles resulted in a significant lethal effect after neutron radiation due to efficient and CD133-independent cellular targeting and uptake in CD133-expressing GSCs. A significantly longer survival occurred in combination with the biconjugate nanoparticles and BSH compared with BSH alone in human intracranial GBM models employing CD133-positive GSCs xenografts. Our data demonstrated that this bioconjugate nanoparticle targets human CD133-positive GSCs and is a potential boron agent in BNCT.

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“…Sugar densities were evaluated for Glu, Gal and Mann by a previously reported method [ 2 , 7 ]. Briefly, Glu-Ag-NPs, Gal-Ag-NPs and Mann-Ag-NPs were dispersed in deionized water (0.5 mL) in an ice bath.…”

Section: Methodsmentioning

confidence: 99%

Carbohydrate functionalization of silver nanoparticles modulates cytotoxicity and cellular uptake

et al. 2014

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BackgroundIncreasing use of silver nanoparticles (Ag-NPs) in various products is resulting in a greater likelihood of human exposure to these materials. Nevertheless, little is still known about the influence of carbohydrates on the toxicity and cellular uptake of nanoparticles.MethodsAg-NPs functionalized with three different monosaccharides and ethylene glycol were synthesized and characterised. Oxidative stress and toxicity was evaluated by protein carbonylation and MTT assay, respectively. Cellular uptake was evaluated by confocal microscopy and ICP-MS.ResultsAg-NPs coated with galactose and mannose were considerably less toxic to neuronal-like cells and hepatocytes compared to particles functionalized by glucose, ethylene glycol or citrate. Toxicity correlated to oxidative stress but not to cellular uptake.ConclusionsCarbohydrate coating on silver nanoparticles modulates both oxidative stress and cellular uptake, but mainly the first has an impact on toxicity. These findings provide new perspectives on modulating the bioactivity of Ag-NPs by using carbohydrates.Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-014-0059-z) contains supplementary material, which is available to authorized users.

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Trivalent galactosyl-functionalized mesoporous silica nanoparticles as a target-specific delivery system for boron neutron capture therapy

Cited by 40 publications

References 50 publications

Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers

Functionalized mesoporous silica nanoparticles for innovative boron-neutron capture therapy of resistant cancers

Targeting glioma stem cells enhances anti-tumor effect of boron neutron capture therapy

Carbohydrate functionalization of silver nanoparticles modulates cytotoxicity and cellular uptake

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