The effectiveness of a magnetic nanoparticle-based delivery system for BCNU in the treatment of gliomas

Hua, Mu-Yi; Liu, Hao-Li; Yang, Hung-Wei; Chen, Pin-Yuan; Tsai, Rung-Ywan; Huang, Chiung-Yin; Tseng, I-Fan; Lyu, Lee-Ang; Ma, Chih-Chun; Tang, Hsiang-Jun; Yen, Tzu‐Chen; Wei, Kuo‐Chen

doi:10.1016/j.biomaterials.2010.09.065

Cited by 141 publications

(83 citation statements)

References 47 publications

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“…[1][2][3] From the past few decades, nanosized iron oxide particles have attracted great attention in the fields including, but not limited to, immunoassay, 4,5 biosensor, 6,7 bioseparation, 8,9 targeted drug delivery, 10,11 and environmental analysis 12,13 and protein immobilization. [14][15][16][17][18][19][20][21] However, the bare Fe 3 O 4 NPs have high reactivity and easily undergo degradation upon direct exposing to certain environment, leading to poor stability and dispersity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Magnetic Nanoparticles and Its Application in Lipase Immobilization

Xu¹,

Ju²,

Sheng³

et al. 2013

Bulletin of the Korean Chemical Society

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We demonstrate herein the synthesis and modification of magnetic nanoparticles and its use in the immobilization of the lipase. Magnetic Fe 3 O 4 nanoparticles (MNPs) were prepared by simple co-precipitation method in aqueous medium and then subsequently modified with tetraethyl orthosilicate (TEOS) and 3-aminopropyl triethylenesilane (APTES). Silanization magnetic nanoparticles (SMNP) and amino magnetic nanomicrosphere (AMNP) were synthesized successfully. The morphology, structure, magnetic property and chemical composition of the synthetic MNP and its derivatives were characterized using transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) analysis, X-ray diffraction, superconducting quantum interference device (SQUID) and thermogravimetric analyses (TGA). All of these three nanoparticles exhibited good crystallization performance, apparent superparamagnetism, and the saturation magnetization of MNP, SMNP, AMNP were 47.9 emu/g, 33.0 emu/g and 19.5 emu/g, respectively. The amino content was 5.66%. The AMNP was used to immobilize lipase, and the maximum adsorption capacity of the protein was 26.3 mg/g. The maximum maintained activity (88 percent) was achieved while the amount of immobilized lipase was 23.7 mg g −1. Immobilization of enzyme on the magnetic nanoparticles can facilitate the isolation of reaction products from reaction mixture and thus lowers the cost of enzyme application.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Magnetic Nanoparticles and Its Application in Lipase Immobilization

Xu¹,

Ju²,

Sheng³

et al. 2013

Bulletin of the Korean Chemical Society

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“…4). Hua et al 28 similarly demonstrated the success of using magnetic targeting to deliver MNP-BCNU ( Fig. 2A) into the brain tumor implant animal cells to confirm the effectiveness of the designed highly magnetized MNP.…”

Section: Therapeutic Mnps For Fus-enhanced Deliverymentioning

confidence: 81%

“…Magnetic targeting of MNP-BCNU led to a significant reduction in the IC 50 to only 4.3 mg/ml (Fig. 2C), 28 suggesting that more of the MNP-BCNU was effectively guided to and concentrated at the target area.…”

Section: Dose-dependent Therapeutic Mnps: In Vitro Considerationsmentioning

confidence: 98%

Enhanced therapeutic agent delivery through magnetic resonance imaging–monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status

Liu

Yang

Hua

et al. 2012

FOC

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Malignant glioma is a severe primary CNS cancer with a high recurrence and mortality rate. The current strategy of surgical debulking combined with radiation therapy or chemotherapy does not provide good prognosis, tumor progression control, or improved patient survival. The blood-brain barrier (BBB) acts as a major obstacle to chemotherapeutic treatment of brain tumors by severely restricting drug delivery into the brain. Because of their high toxicity, chemotherapeutic drugs cannot be administered at sufficient concentrations by conventional delivery methods to significantly improve long-term survival of patients with brain tumors. Temporal disruption of the BBB by microbubble-enhanced focused ultrasound (FUS) exposure can increase CNS-blood permeability, providing a promising new direction to increase the concentration of therapeutic agents in the brain tumor and improve disease control. Under the guidance and monitoring of MR imaging, a brain drug-delivery platform can be developed to control and monitor therapeutic agent distribution and kinetics. The success of FUS BBB disruption in delivering a variety of therapeutic molecules into brain tumors has recently been demonstrated in an animal model. In this paper the authors review a number of critical studies that have demonstrated successful outcomes, including enhancement of the delivery of traditional clinically used chemotherapeutic agents or application of novel nanocarrier designs for actively transporting drugs or extending drug half-lives to significantly improve treatment efficacy in preclinical animal models.

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“…The drug activities were analyzed using the Bratton-Marshall assay. 27,28 Forty microliters of free BCNU and PAA-GO-BCNU solution were reacted with 80 µL of sulfanilamide solution (5 mg/mL in 2 M HCl) at 50°C for 45 minutes and then cooled to room temperature. One hundred microliters of the above solution and 10 µL of Bratton-Marshall reagent (3 mg/mL of N-(1-naphthyl) ethylenediamine in deionized water) were reacted for one minute and absorbances were measured at 540 nm using a Genesys 20 spectrophotometer (Thermo Scientific, Barrington IL).…”

Section: Thermal Stability Study Of Bcnumentioning

confidence: 99%

Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide

Yang²,

Hung³

et al. 2012

IJN

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Background: 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), a commercial chemotherapeutic drug for treating malignant brain tumors, has poor thermal stability and a short half-life. Immobilization of BCNU on a nanocarrier might increase the thermal stability of BCNU and extend its half-life. Methods: Nanosized graphene oxide (GO) could be modified by polyacrylic acid (PAA) to improve the aqueous solubility and increase the cell penetration efficacy of the nanocarrier. PAA-GO intended as a drug carrier for BCNU was prepared and characterized in this study. The size and thickness of PAA-GO was investigated by transmission electron microscopy and atomic force microscopy, and the presence of PAA functional groups was confirmed by electron spectroscopy for chemical analysis and thermogravimetric analysis. BCNU was conjugated to PAA-GO by covalent binding for specific killing of cancer cells, which could also enhance the thermal stability of the drug. Results: Single layer PAA-GO (about 1.9 nm) with a lateral width as small as 36 nm was successfully prepared. The optimum drug immobilization condition was by reacting 0.5 mg PAA-GO with 0.4 mg BCNU, and the drug-loading capacity and residual drug activity were 198 µg BCNU/mg PAA-GO and 70%, respectively. This nanocarrier significantly prolonged the half-life of bound BCNU from 19 to 43 hours compared with free drug and showed efficient intracellular uptake by GL261 cancer cells. The in vitro anticancer efficacy of PAA-GO-BCNU was demonstrated by a 30% increase in DNA interstrand cross-linking and a 77% decrease in the IC 50 value toward GL261 compared with the same dosage of free drug. Conclusion: Nanosized PAA-GO serves as an efficient BCNU nanocarrier by covalent binding. This nanocarrier will be a promising new vehicle for an advanced drug delivery system in cancer therapy.

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The effectiveness of a magnetic nanoparticle-based delivery system for BCNU in the treatment of gliomas

Cited by 141 publications

References 47 publications

Synthesis and Characterization of Magnetic Nanoparticles and Its Application in Lipase Immobilization

Synthesis and Characterization of Magnetic Nanoparticles and Its Application in Lipase Immobilization

Enhanced therapeutic agent delivery through magnetic resonance imaging–monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status

Improving thermal stability and efficacy of BCNU in treating glioma cells using PAA-functionalized graphene oxide

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