Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy

Dilnawaz, Fahima; Singh, Abhalaxmi; Mohanty, Chandana; Sahoo, Sanjeeb K.

doi:10.1016/j.biomaterials.2010.01.057

Cited by 360 publications

(253 citation statements)

References 52 publications

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“…The MNPs studied here are nontoxic to ocular structures when studied in mice (62). Magnetic forces can target MNPs to specific cellular populations (63) and release MNP encapsulated therapeutics at target sites (64). Our result showing that fMNPs that stimulate neurite growth can be endocytosed into RGC cells bodies and then transported anterogradely in neurites both in vitro and in vivo support methods for targeting nanotherapeutics to inaccessible regions of the CNS.…”

Section: Discussionsupporting

confidence: 53%

Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth

Steketee

Moysidis

Jin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Understanding neurite growth regulation remains a seminal problem in neurobiology. During development and regeneration, neurite growth is modulated by neurotrophin-activated signaling endosomes that transmit regulatory signals between soma and growth cones. After injury, delivering neurotrophic therapeutics to injured neurons is limited by our understanding of how signaling endosome localization in the growth cone affects neurite growth. Nanobiotechnology is providing new tools to answer previously inaccessible questions. Here, we show superparamagnetic nanoparticles (MNPs) functionalized with TrkB agonist antibodies are endocytosed into signaling endosomes by primary neurons that activate TrkB-dependent signaling, gene expression and promote neurite growth. These MNP signaling endosomes are trafficked into nascent and existing neurites and transported between somas and growth cones in vitro and in vivo. Manipulating MNP-signaling endosomes by a focal magnetic field alters growth cone motility and halts neurite growth in both peripheral and central nervous system neurons, demonstrating signaling endosome localization in the growth cone regulates motility and neurite growth. These data suggest functionalized MNPs may be used as a platform to study subcellular organelle localization and to deliver nanotherapeutics to treat injury or disease in the central nervous system. axon | nanotechnology C entral nervous system (CNS) neurons fail to regenerate after injury or disease because of reduced intrinsic axon growth ability (1, 2), inhibitory molecules (3-6), and deficient neurotrophic factor signaling (7-9). Neurotrophins, like brain-derived neurotrophic factor (BDNF), activate tropomyosin-related kinase B (TrkB) receptors and are endocytosed by clathrin-dependent and -independent mechanisms into signaling endosomes (10, 11). These signaling endosomes signal persistently during retrograde (12) and anterograde (13, 14) transport in axons or dendrites (15, 16) directing neurite growth, survival, and cell migration (17, 18). Signaling endosomes are critical long-range communication links used by neurons in the central and peripheral nervous system during development and regeneration (17), whose dysfunction is linked to nervous system disorders (19-21). Therefore, studying signaling endosome localization and related functions in regulating neurite growth is vital. MNPs are emerging as flexible, multimodal nanoparticles that can be targeted to specific tissues or cells by molecular functionalization. To alter signaling endosome localization, we targeted functionalized MNPs to active TrkB signaling endosomes and demonstrate that magnetically manipulating their localization affects growth cone behavior and neurite growth. ResultsTo load MNPs into TrkB signaling endosomes, 50-nm MNPs were functionalized with the anti-TrkB agonist antibody, 29D7, conjugated to Alexa 594. 29D7 activates TrkB and enhances retinal ganglion cell (RGC) survival and neurite growth in vitro and in vivo (22). Now, we show 29D7 facilitates rapid MNP e...

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Section: Discussionsupporting

confidence: 53%

Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth

Steketee

Moysidis

Jin

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Magnetic nanoparticles are actively being developed based on their unique properties responsive to magnetic fields, including magnetic hyperthermia and MRI contrast agent. [15][16][17][18] Active targeting for superficial tumors can also be performed using magnetic fields. [19][20][21][22] This strategy has been tested in patients with advanced stages of cancer.…”

Section: Introductionmentioning

confidence: 99%

Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy

Liang

Chen

Chiang

et al. 2016

IJN

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In this study, we developed functionalized superparamagnetic iron oxide (SPIO) nanoparticles consisting of a magnetic Fe 3 O 4 core and a shell of aqueous stable polyethylene glycol (PEG) conjugated with doxorubicin (Dox) (SPIO-PEG-D) for tumor magnetic resonance imaging (MRI) enhancement and chemotherapy. The size of SPIO nanoparticles was ~10 nm, which was visualized by transmission electron microscope. The hysteresis curve, generated with vibrating-sample magnetometer, showed that SPIO-PEG-D was superparamagnetic with an insignificant hysteresis. The transverse relaxivity ( r 2 ) for SPIO-PEG-D was significantly higher than the longitudinal relaxivity ( r 1 ) ( r 2 / r 1 >10). The half-life of Dox in blood circulation was prolonged by conjugating Dox on the surface of SPIO with PEG to reduce its degradation. The in vitro experiment showed that SPIO-PEG-D could cause DNA crosslink more serious, resulting in a lower DNA expression and a higher cell apoptosis for HT-29 cancer cells. The Prussian blue staining study showed that the tumors treated with SPIO-PEG-D under a magnetic field had a much higher intratumoral iron density than the tumors treated with SPIO-PEG-D alone. The in vivo MRI study showed that the T 2 -weighted signal enhancement was stronger for the group under a magnetic field, indicating that it had a better accumulation of SPIO-PEG-D in tumor tissues. In the anticancer efficiency study for SPIO-PEG-D, the results showed that there was a significantly smaller tumor size for the group with a magnetic field than the group without. The in vivo experiments also showed that this drug delivery system combined with a local magnetic field could reduce the side effects of cardiotoxicity and hepatotoxicity. The results showed that the developed SPIO-PEG-D nanoparticles own a great potential for MRI-monitoring magnet-enhancing tumor chemotherapy.

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“…Different concentrations of IRAK1/4 inhibitor and ABT-737 in solution and in IRAK/ABT-NP were tested. 25 Jurkat cells were seeded in 96-well plates and incubated for 24 hours. The cells were treated with each concentration of drugs and incubated for 48 hours.…”

Section: Cytotoxicity Studymentioning

confidence: 99%

Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia

Wu¹,

Wang²,

Qiu³

et al. 2017

IJN

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T cell acute lymphoblastic leukemia (T-ALL) is caused by clonal expansion of variant T cell progenitors and is considered as a high risk leukemia. Contemporary single chemotherapy has a limited effect due to dynamic and versatile properties of T-ALL. Here IRAK1/4 inhibitor and ABT-737 were co-encapsulated into polyethylene glycol modified poly (lactic-co-glycolic acid) nanoparticles (IRAK/ABT-NP) to enhance synergistic therapy of T-ALL. The formulation was optimized to achieve high drug loading using Box-Behnken design and response surface methodology. The optimal parameter comprised 2.98% polymer in acetonitrile, a ratio of oil phase to water phase of 1:8.33, and 2.12% emulsifier concentration. High drug loading and uniform spherical shape was achieved. In vitro release study showed sustained release of IRAK1/4 inhibitor for 72 hours as well as sustained release of ABT-737 for more than 120 hours. Uptake efficiency of IRAK/ABT-NP and induced apoptotic T-ALL fraction by IRAK/ABT-NP were much higher than the IRAK1/4 and ABT-737 combined solution. IC 50 of IRAK/ABT-NP was two-fold lower than free drug combination in Jurkat cells. Additionally, we conducted in vivo experiments in which IRAK/ABT-NP exhibited greater cytotoxicity toward T-ALL cells, the capacity to significantly restore white blood cell number in peripheral blood, and improved survival time of T-ALL mouse model compared to the IRAK1/4 and ABT-737 combined solution.

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Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy

Cited by 360 publications

References 52 publications

Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth

Nanoparticle-mediated signaling endosome localization regulates growth cone motility and neurite growth

Doxorubicin-modified magnetic nanoparticles as a drug delivery system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy

Cooperation of IRAK1/4 inhibitor and ABT-737 in nanoparticles for synergistic therapy of T cell acute lymphoblastic leukemia

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