Lysosomal Membrane Permeabilization by Targeted Magnetic Nanoparticles in Alternating Magnetic Fields

Domenech, Maribella; Marrero-Berríos, Ileana; Torres‐Lugo, Madeline; Rinaldi, Carlos

doi:10.1021/nn4007048

Cited by 227 publications

(242 citation statements)

References 52 publications

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“…Surface areas are commonly decorated with coatings that are intended for two purposes: to enhance the biocompatibility of the nanoparticle and to gain bioactivity, ie, to become an active player in the biological niche of interest. This bioactivity has been exploited for cell targeting, 2,3 cargo payload (drug and gene delivery), [4][5][6] contrast agents, 7 or a combination of these, giving multifunctionality to a nanostructure. [8][9][10] Magnetic nanoparticles (MNPs) can be remotely manipulated by magnetic fields.…”

Section: Introductionmentioning

confidence: 99%

Non-chemotoxic induction of cancer cell death using magnetic nanowires

Contreras¹,

Sougrat²,

Zaher³

et al. 2015

IJN

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In this paper, we show that magnetic nanowires with weak magnetic fields and low frequencies can induce cell death via a mechanism that does not involve heat production. We incubated colon cancer cells with two concentrations (2.4 and 12 μg/mL) of nickel nanowires that were 35 nm in diameter and exposed the cells and nanowires to an alternating magnetic field (0.5 mT and 1 Hz or 1 kHz) for 10 or 30 minutes. This low-power field exerted a force on the magnetic nanowires, causing a mechanical disturbance to the cells. Transmission electron microscopy images showed that the nanostructures were internalized into the cells within 1 hour of incubation. Cell viability studies showed that the magnetic field and the nanowires separately had minor deleterious effects on the cells; however, when combined, the magnetic field and nanowires caused the cell viability values to drop by up to 39%, depending on the strength of the magnetic field and the concentration of the nanowires. Cell membrane leakage experiments indicated membrane leakage of 20%, suggesting that cell death mechanisms induced by the nanowires and magnetic field involve some cell membrane rupture. Results suggest that magnetic nanowires can kill cancer cells. The proposed process requires simple and low-cost equipment with exposure to only very weak magnetic fields for short time periods.

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Section: Introductionmentioning

confidence: 99%

Non-chemotoxic induction of cancer cell death using magnetic nanowires

Contreras¹,

Sougrat²,

Zaher³

et al. 2015

IJN

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“…Furthermore, high intracellular calcium levels caused by NPs may also serve as an alternative mechanism for the activation of these mechanisms. 84 Domenech et al 85 found that IO MNPs are capable of inducing lysosome LMP in cells. Yang et al 86 used both acridine orange staining and transmission electron microscopy (TEM) images to confirm that the accumulation of carbon nanohorns (CNHs) in the lysosomes induced LMP.…”

mentioning

confidence: 99%

Central nervous system toxicity of metallic nanoparticles

Feng¹,

Chen²,

Zhang³

et al. 2015

IJN

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Nanomaterials (NMs) are increasingly used for the therapy, diagnosis, and monitoring of disease- or drug-induced mechanisms in the human biological system. In view of their small size, after certain modifications, NMs have the capacity to bypass or cross the blood–brain barrier. Nanotechnology is particularly advantageous in the field of neurology. Examples may include the utilization of nanoparticle (NP)-based drug carriers to readily cross the blood–brain barrier to treat central nervous system (CNS) diseases, nanoscaffolds for axonal regeneration, nanoelectromechanical systems in neurological operations, and NPs in molecular imaging and CNS imaging. However, NPs can also be potentially hazardous to the CNS in terms of nano-neurotoxicity via several possible mechanisms, such as oxidative stress, autophagy, and lysosome dysfunction, and the activation of certain signaling pathways. In this review, we discuss the dual effect of NMs on the CNS and the mechanisms involved. The limitations of the current research are also discussed.

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“…20 Recent studies have shown that hyperthermia using a water bath interrupts protein homeostasis in the cell. 18 Taking into account the fact that MFH produces marked effects on the cell as shown by recent studies, 27,35 one potential cause of this enhanced cytotoxicity could be related to increased production of unfolded proteins and their subsequent aggregation induced by heat delivered by the magnetic nanoparticles, drastically affecting protein homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines

Alvarez-Berríos¹,

Castillo²,

Rinaldi³

et al. 2013

IJN

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The proteasome inhibitor bortezomib (BZ) has shown promising results in some types of cancer, but in others it has had minimal activity. Recent studies have reported enhanced efficacy of BZ when combined with hyperthermia. However, the use of magnetic nanoparticles to induce hyperthermia in combination with BZ has not been reported. This novel hyperthermia modality has shown better potentiation of chemotherapeutics over other types of hyperthermia. We hypothesized that inducing hyperthermia via magnetic nanoparticles (MFH) would enhance the cytotoxicity of BZ in BZ-sensitive and BZ-resistant cancer cells more effectively than hyperthermia using a hot water bath (HWH). Studies were conducted using BZ in combination with MFH in two BZ-sensitive cell lines (MDA-MB-468, Caco-2), and one BZ-resistant cell line (A2780) at two different conditions, ie, 43°C for 30 minutes and 45°C for 30 minutes. These experiments were compared with combined application of HWH and BZ. The results indicate enhanced potentiation between hyperthermic treatment and BZ. MFH combined with BZ induced cytotoxicity in sensitive and resistant cell lines to a greater extent than HWH under the same treatment conditions. The observation that MFH sensitizes BZ-resistant cell lines makes this approach a potentially effective anticancer therapy platform.

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Lysosomal Membrane Permeabilization by Targeted Magnetic Nanoparticles in Alternating Magnetic Fields

Cited by 227 publications

References 52 publications

Non-chemotoxic induction of cancer cell death using magnetic nanowires

Non-chemotoxic induction of cancer cell death using magnetic nanowires

Central nervous system toxicity of metallic nanoparticles

Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines

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