SPECT/CT imaging of radiolabeled cubosomes and hexosomes for potential theranostic applications

Nilsson, Christa; Barrios-Lopez, Brianda; Kallinen, Annukka; Laurinmäki, Pasi; Butcher, Sarah J.; Raki, Mari; Weisell, Janne; Bergström, Kim A.; Larsen, Susan Weng; Østergaard, Jesper; Larsen, Claus; Urtti, Arto; Airaksinen, Anu J.; Yaghmur, Anan

doi:10.1016/j.biomaterials.2013.07.055

Cited by 71 publications

(59 citation statements)

References 64 publications

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“…The occurrence of the H 2 phase was unexpected because previous studies reported on the formation of PHYT cubosomes with a neat internal nanostructure of the cubic Pn3m phase at ambient temperature. 6,15,32 These discrepancies may be due to the presence of impurities in this commercial batch of PHYT, which could account for the formation of the internal biphasic nanostructure as recently indicated. 15 The mentioned impurities may include a tiny amount of water (about 0.07%), sulfated ash, heavy metals, and a diastereomer of phytantriol (3,7,11,15-tetramethyl-1,2,3,4-tetrahydroxyhexadecane), which is a compound that differs from PHYT in that it has a hydroxy group in position 4, resulting in five chiral C atoms, as opposed to four chiral C atoms in PHYT.…”

Section: Structural Investigation Of Phyt-based Aqueousmentioning

confidence: 91%

“…6,15,32 These discrepancies may be due to the presence of impurities in this commercial batch of PHYT, which could account for the formation of the internal biphasic nanostructure as recently indicated. 15 The mentioned impurities may include a tiny amount of water (about 0.07%), sulfated ash, heavy metals, and a diastereomer of phytantriol (3,7,11,15-tetramethyl-1,2,3,4-tetrahydroxyhexadecane), which is a compound that differs from PHYT in that it has a hydroxy group in position 4, resulting in five chiral C atoms, as opposed to four chiral C atoms in PHYT. Furthermore, subtle levels of impurities in PHYT have been suggested to have a significant effect on the temperaturedependent phase behavior of the binary PHYT/water system.…”

Section: Structural Investigation Of Phyt-based Aqueousmentioning

confidence: 91%

“…11−14 Furthermore, these assemblies have great potential for biosensing as well as engineering tunable diagnostic/contrast agents for imaging modalities such as singlephoton emission computed tomography/computed tomography and magnetic resonance. 15 −17 On exposure to blood, nanoparticles and vesicular systems, depending on their curvature, shape, and surface characteristics, attract a wide range of plasma proteins. 18−20 Plasma protein deposition is believed to be a dynamic event and may control the biological performance of nanoparticles, including their stability in the blood, in pharmacokinetics, and in tissue distribution.…”

Section: Introductionmentioning

confidence: 99%

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Modulatory Effect of Human Plasma on the Internal Nanostructure and Size Characteristics of Liquid-Crystalline Nanocarriers

Azmi¹,

Wu²,

Wibroe³

et al. 2015

Langmuir

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The inverted-type liquid-crystalline dispersions comprising cubosomes and hexosomes hold much potential for drug solubilization and site-specific targeting on intravenous administration. Limited information, however, is available on the influence of plasma components on nanostructural and morphological features of cubosome and hexosome dispersions, which may modulate their stability in the blood and their overall biological performance. Through an integrated approach involving SAXS, cryo-TEM, and nanoparticle tracking analysis (NTA) we have studied the time-dependent effect of human plasma (and the plasma complement system) on the integrity of the internal nanostructure, morphology, and fluctuation in size distribution of phytantriol (PHYT)-based nonlamellar crystalline dispersions. The results indicate that in the presence of plasma the internal nanostructure undergoes a transition from the biphasic phase (a bicontinuous cubic phase with symmetry Pn3m coexisting with an inverted-type hexagonal (H2) phase) to a neat hexagonal (H2) phase, which decreases the median particle size. These observations were independent of a direct effect by serum albumin and dispersion-mediated complement activation. The implication of these observations in relation to soft nanocarrier design for intravenous drug delivery is discussed.

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Section: Structural Investigation Of Phyt-based Aqueousmentioning

confidence: 91%

Section: Structural Investigation Of Phyt-based Aqueousmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modulatory Effect of Human Plasma on the Internal Nanostructure and Size Characteristics of Liquid-Crystalline Nanocarriers

Azmi¹,

Wu²,

Wibroe³

et al. 2015

Langmuir

Self Cite

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“…25. 34 Taking the result of a recent report into account, 35 the peak corresponded primarily to the first diffraction peak from the inverted 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 11 H 2 phase. The co-existence of cubic Pn3m and inverted H 2 phases might be attributable to the presence of impurities of commercial lipid phytantriol used in this study.…”

Section: Resultsmentioning

confidence: 94%

A Simple Evaporation Method for Large-Scale Production of Liquid Crystalline Lipid Nanoparticles with Various Internal Structures

Kim

Lim

Shim

et al. 2015

ACS Appl. Mater. Interfaces

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We present a simple and industrially accessible method of producing liquid crystalline lipid nanoparticles with various internal structures based on phytantriol, Pluronic F127, and vitamin E acetate. Bilayer vesicles were produced when an ethanolic solution dissolving the lipid components was mixed with deionized water. After the evaporation of ethanol from the aqueous mixture, vesicles were transformed into lipid-filled liquid crystalline nanoparticles with well-defined internal structures such as hexagonal lattices (mostly inverted cubic Pn3m), lined or coiled pattern (inverted hexagonal H2), and disordered structure (inverse microemulsion, L2), depending on the compositions. Further studies suggested that their internal structures were also affected by temperature. The internal structures were characterized from cryo-TEM and small-angle X-ray scattering results. Microcalorimetry studies were performed to investigate the degree of molecular ordering/crystallinity of lipid components within the nanostructures. From the comparative studies, we demonstrated the present method could produce the lipid nanoparticles with similar characteristics to those made from a conventional method. More importantly, the production only requires simple tools for mixing and ethanol evaporation and it is possible to produce 10 kg or so per batch of aqueous lipid nanoparticles dispersions, enabling the large-scale production of the liquid crystalline nanoparticles for various biomedical applications.

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“…Other few examples of theranostic nanoparticles with a stable mesophase structure such as hexosomes or cubosomes have been recently reported. [35][36][37][38] Murgia et al described monolein based cubosomes able to encapsulate anticancer drugs such as quercitin or camptotechin and a NIR-emitting fluorescent probe together with the targetselective theranostic analogue modified with a folatepluronic derivative. 35 36 The in vitro binding properties on HeLa cells of these theranostic cubosomes were investigated.…”

Section: Discussionmentioning

confidence: 98%

Diolein Based Nanostructures as Targeted Theranostics

Accardo¹,

Arena²,

Gianolio³

et al. 2016

j biomed nanotechnol

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Diolein based non-targeted theranostic nanoparticles (DO-NPs) containing 10%wt of the amphiphilic Gadolinium complex (C18)2DTPA(Gd), and targeted NPs, obtained by introducing growing amounts (3% wt, 6% wt or 10% wt) of (C18)2-Peg3000- FA in the sample composition, have been studied for their in vitro and in vivo properties. Cellular binding was studied by lCP-MS analysis of the Gadolinium content and by Surface Plasmon Resonance (SPR) assays. The best formulation in terms of selectivity towards IGROV-1 cells with respect to non-targeted DO-NPs, was that containing 3% (C18)2Peg3000- FA (P < 0.01). Cytotoxic studies and confocal microscopy analysis of IGROV-1 cells indicate high selective properties of the targeted doxorubicin (DOX) loaded NPs. Nanoparticles described here represent the first example in which a targeted carrier characterized by a stable foamy mesophase, provided by the Diolein component, combine the therapeutic effect due to the anticancer drug doxorubicin, with the imaging properties provided by paramagnetic gadolinium complexes for MRI. As evidenced by T(1w), and T(2w) MRI images and by the in vivo antitumor effect in IGROV-1 tumor-bearing mice, DO-NP3-FA/DOX provides very high therapeutic efficacy with a tumor growth regression of 80% and 50% higher as compared to the mice treated with saline solution and with Doxil, respectively.

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SPECT/CT imaging of radiolabeled cubosomes and hexosomes for potential theranostic applications

Cited by 71 publications

References 64 publications

Modulatory Effect of Human Plasma on the Internal Nanostructure and Size Characteristics of Liquid-Crystalline Nanocarriers

Modulatory Effect of Human Plasma on the Internal Nanostructure and Size Characteristics of Liquid-Crystalline Nanocarriers

A Simple Evaporation Method for Large-Scale Production of Liquid Crystalline Lipid Nanoparticles with Various Internal Structures

Diolein Based Nanostructures as Targeted Theranostics

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