Magnetoliposomes with high USPIO entrapping efficiency, stability and magnetic properties

Σκούρας, Αθανάσιος; Mourtas, Spyridon; Markoutsa, Eleni; Goltstein, Marie-Christine De; Wallon, Claire; Catoen, Sarah; Antimisiaris, Sophia G.

doi:10.1016/j.nano.2011.06.010

Cited by 59 publications

(39 citation statements)

References 29 publications

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“…Regardless of this fact, the absolute amount of iron that could be incorporated into liposomes was higher using higher initial amounts of USPIOs. This finding is in accordance with results reported by Skouras et al 30 Further increases in iron concentration (above 3 mg Fe/mL) did not improve the absolute yield (data not shown).…”

Section: Stealth Magnetic Liposome Purification and Encapsulation Effsupporting

confidence: 93%

Ultrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes

Frascione¹,

Almer²,

Opriessnig³

et al. 2012

IJN

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Background: Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magnetic and/or paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI). MLs have an advantage over free magnetic nanocores, in that various functional groups can be attached to the surface of liposomes for ligand-specific targeting. We have synthesized PEG-coated sterically-stabilized magnetic liposomes (sMLs) containing ultrasmall superparamagnetic iron oxides (USPIOs) with the aim of generating stable liposomal carriers equipped with a high payload of USPIOs for enhanced MRI contrast. Methods: Regarding iron oxide nanoparticles, we have applied two different commercially available surface-coated USPIOs; sMLs synthesized and loaded with USPIOs were compared in terms of magnetization and colloidal stability. The average diameter size, morphology, phospholipid membrane fluidity, and the iron content of the sMLs were determined by dynamic light scattering (DLS), transmission electron microscopy (TEM), fluorescence polarization, and absorption spectroscopy, respectively. A colorimetric assay using potassium thiocyanate (KSCN) was performed to evaluate the encapsulation efficiency (EE%) to express the amount of iron enclosed into a liposome. Subsequently, MRI measurements were carried out in vitro in agarose gel phantoms to evaluate the signal enhancement on T1-and T2-weighted sequences of sMLs. To monitor the biodistribution and the clearance of the particles over time in vivo, sMLs were injected in wild type mice. Results: DLS revealed a mean particle diameter of sMLs in the range between 100 and 200 nm, as confirmed by TEM. An effective iron oxide loading was achieved just for one type of USPIO, with an EE% between 74% and 92%, depending on the initial Fe concentration (being higher for lower amounts of Fe). MRI measurements demonstrated the applicability of these nanostructures as MRI probes. Conclusion: Our results show that the development of sMLs is strictly dependent on the physicochemical characteristics of the nanocores. Once established, sMLs can be further modified to enable noninvasive targeted molecular imaging.

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Section: Stealth Magnetic Liposome Purification and Encapsulation Effsupporting

confidence: 93%

Ultrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes

Frascione¹,

Almer²,

Opriessnig³

et al. 2012

IJN

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“…USPIOs are colloidal particles and it proved difficult to achieve this goal with a common liposome preparation method, such as the film dispersion method (the EE was less than 15%). 26 In this study, through transient binding and REV method we successfully obtained stable and nonaggregated PEGlyated liposomes with simultaneously loading of USPIOs and DOX, and by a postinsertion method, the anti-MSLN antibody was successfully conjugated to the terminus of PEG chain on the liposome surface. The scheme for constructing anti-MSLN-conjugated PEGylated liposomes was presented in Figure 1.…”

Section: Characterization Of M-pldusmentioning

confidence: 99%

A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer

Deng¹,

Ke²,

He³

et al. 2012

IJN

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Pancreatic cancer is a highly lethal disease with a 5-year survival rate less than 5% due to the lack of an early diagnosis method and effective therapy. To provide a novel early diagnostic method and targeted therapy for pancreatic cancer, a multifunctional nanoimmunoliposome with high loading of ultrasmall superparamagnetic iron oxides (USPIOs) and doxorubicin (DOX) was prepared by transient binding and reverse-phase evaporation method, and was conjugated with anti-mesothelin monoclonal antibody by post-insertion method to target anti-mesothelin-overexpressed pancreatic cancer cells. The in vitro and in vivo properties of this anti-mesothelin antibody-conjugated PEGlyated liposomal DOX and USPIOs (M-PLDU; and PEGlyated nanoimmunoliposome without antibody conjugation [PLDU]) were evaluated both in human pancreatic cancer cell line Panc-1 cell and in a pancreatic cancer xenograft animal model. Results showed that M-PLDUs were spherical and uniform with a diameter about ∼180 nm, with a zeta potential of about −28∼−30 mV, and had good efficacy encapsulating DOX and USPIOs. The in vitro study demonstrated that M-PLDUs possessed good magnetic resonance imaging (MRI) capability with a transverse relaxivity (r 2 ) of about 58.5 mM -1 ⋅ s -1 . Confocal microscopy showed more efficient uptake of M-PLDU in Panc-1 cells by antibodymediated targeting. Methyl thiazolyl tetrazolium assay results showed significant inhibitory effect of M-PLDU against Panc-1 cells (half-maximal inhibitory concentration, 1.95 µM). The in vivo imaging study showed that the tumor signal intensity (SI) dropped significantly about 4 hours after intravenous injection of M-PLDU. The decrease in tumor SI induced by M-PLDUs (∆SI = 145.98 ± 20.45) or PLDUs (∆SI = 75.69 ± 14.53) was much more significant than that by free USPIOs (∆SI = 42.78 ± 22.12; P , 0.01). The in vivo antitumor study demonstrated that compared with FD (free DOX) and PLDU, M-PLDU possessed higher inhibitory effect on tumor growth and the tissue distribution assay further proved that M-PLDUs could selectively accumulate in the tumor xenograft. These results indicated that M-PLDU not only well retained the inherent MRI capability of USPIOs, but significantly improved the targeting distribution of USPIOs and therapeutic agents in pancreatic tumor tissues. They may serve as a promising theranostic nanomedicine not only for early detection but also for MRI-monitored targeting therapy of human pancreatic cancer.

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“…26 Much progress has also been made in developing better quality magnetic nanoparticles that: are constructed using high temperature crystallization; 27 heat better; 28,29 have different coatings, such as dextran, 30,31 polyethylene glycol (PEG), 32 dopamine, 33 silanes, 34 and gold; 35,36 have low Curie temperatures for heat control; 37 and for liposomal encapsulation. 17,[38][39][40] Direct intratumoral injections of MNPs followed by induction heating has shown some benefit in controlling tumor growth. 38,[41][42][43][44][45][46][47][48][49] Direct intratumoral injection was used in the first MNP hyperthermia clinical trial treating a prostate cancer using a 100 kHz machine designed for human patients, 50 and later in human glioma trials 51,52 which demonstrated safety and some benefit.…”

Section: Introductionmentioning

confidence: 99%

Intravenous magnetic nanoparticle cancer hyperthermia

Huang¹,

Hainfeld²

2013

IJN

104

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Magnetic nanoparticles heated by an alternating magnetic field could be used to treat cancers, either alone or in combination with radiotherapy or chemotherapy. However, direct intratumoral injections suffer from tumor incongruence and invasiveness, typically leaving undertreated regions, which lead to cancer regrowth. Intravenous injection more faithfully loads tumors, but, so far, it has been difficult achieving the necessary concentration in tumors before systemic toxicity occurs. Here, we describe use of a magnetic nanoparticle that, with a well-tolerated intravenous dose, achieved a tumor concentration of 1.9 mg Fe/g tumor in a subcutaneous squamous cell carcinoma mouse model, with a tumor to non-tumor ratio . 16. With an applied field of 38 kA/m at 980 kHz, tumors could be heated to 60°C in 2 minutes, durably ablating them with millimeter (mm) precision, leaving surrounding tissue intact.

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Magnetoliposomes with high USPIO entrapping efficiency, stability and magnetic properties

Cited by 59 publications

References 29 publications

Ultrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes

Ultrasmall superparamagnetic iron oxide (USPIO)-based liposomes as magnetic resonance imaging probes

A MSLN-targeted multifunctional nanoimmunoliposome for MRI and targeting therapy in pancreatic cancer

Intravenous magnetic nanoparticle cancer hyperthermia

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