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WO2013001451A1 - Vecteur pour la libération d'un composant actif qui est photoclivable par irradiation dans le visible - Google Patents

Vecteur pour la libération d'un composant actif qui est photoclivable par irradiation dans le visible Download PDF

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Publication number
WO2013001451A1
WO2013001451A1 PCT/IB2012/053220 IB2012053220W WO2013001451A1 WO 2013001451 A1 WO2013001451 A1 WO 2013001451A1 IB 2012053220 W IB2012053220 W IB 2012053220W WO 2013001451 A1 WO2013001451 A1 WO 2013001451A1
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WIPO (PCT)
Prior art keywords
active agent
surfactant
vector according
group
peptide
Prior art date
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Ceased
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PCT/IB2012/053220
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English (en)
Inventor
Valerio VOLIANI
Stefano LUIN
Riccardo NIFOSI
Fernanda Ricci
Giovanni SIGNORE
Fabio Beltram
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Consiglio Nazionale delle Richerche CNR
Fondazione Istituto Italiano di Tecnologia
Scuola Normale Superiore Di Pisa
Original Assignee
Consiglio Nazionale delle Richerche CNR
Fondazione Istituto Italiano di Tecnologia
Scuola Normale Superiore Di Pisa
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
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Publication of WO2013001451A1 publication Critical patent/WO2013001451A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/008—Two-Photon or Multi-Photon PDT, e.g. with upconverting dyes or photosensitisers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6923—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb

Definitions

  • This invention relates to a vector or device for the administration of an active agent (such as a drug or a label) which is photocleavable with release of the active agent through irradiation with low power light in the visible or near infrared (NIR).
  • an active agent such as a drug or a label
  • NIR near infrared
  • Photocleavable molecules are of great potential interest as tools for diagnosis and treatment, but many unresolved problems stand in the way of the spread of their clinical use.
  • Release vectors for therapeutically active agents comprising organic nanoparticles such as liposomes and lipid nanospheres are known.
  • US 2010/0233224 describes liposome vesicles loaded with a biocide which can release the biocide through irradiation with visible light, which causes rupture of the vesicle's membrane.
  • WO2010/104819 describes a delivery system for a drug mediated by radiation in the near infrared comprising a plurality of microspheres of polymer material in which each sphere contains hollow gold nanospheres together with a pharmaceutically active agent; in this release system the drug is released from the microspheres following NI irradiation.
  • the object of this invention is to provide a new vector for the administration of an active agent (for example a drug) which is not cytotoxic, characterised by high intemalisation in cells and tissues, and capable of releasing the active agent (which has previously been covalently bonded thereto) in situ following irradiation with light in the visible or near infrared (NIR or IR-A (DIN/CIE standard)).
  • an active agent for example a drug
  • NIR or IR-A DIN/CIE standard
  • One object of the invention is a spatially and temporally controlled release vector for an active agent from a nanosystem comprising gold nanoparticles with release induced by superlinear (multiphoton) absorption of light radiation of wavelength greater than 400 nm lying within the region of the visible or the near infrared (NIR) without the need for local increases in temperature for it to function.
  • NIR near infrared
  • the system comprises:
  • the active agent is bound to a colloidal gold particle coated with a surfactant through a group having a photocleavable bond which joins the active agent to a terminal group of the surfactant.
  • the group having a photocleavable bond which can be used within the scope of the invention is an organic molecule which following the absorption of an electromagnetic wave in the visible or NIR breaks into two or more products through the cleavage of one or more covalent bonds.
  • the invention describes vectors designed in such a way as to take advantage of photocleavage through a multiple photon effect in a 1,2,3-triazole system favoured by the increase in the local electromagnetic field induced by the gold nanoparticles (AuNs).
  • Gold nanoparticles preferably having a size of between 20 nm and 60 nm, a size which makes it possible to achieve better cell uptake values, are used; even more preferred are nanoparticles having a size of between 25 nm and 35 nm.
  • the nanoparticles are preferably in the form of nanospheres; however, the shape and size of the nanoparticles are not binding for the purposes of the invention provided that there is a good overlap between the plasmon resonance band of the particle itself and the multiphoton absorption spectrum of the photocleavable part of the molecule responsible for the bond between the metal nanoparticles and the active agent.
  • 30 nm gold nanospheres are used, the choice of these being based on their proven maximum efficiency in terms of cell internalisation and the presence of an extinction band with a peak at 530 nm which has a good overlap with the three-photon absorption spectrum of 1,2,3-triazole rings in a wavelength range comprising 561 nm.
  • the gold nanoparticles may be prepared by reducing a gold salt such as for example hydrogen tetrachloroaurate trihydrate in water, as described in the example which follows.
  • the gold nanoparticles AuNs are covered with a surfactant containing a thiol group which can chemiadsorb onto the surface of the gold particles.
  • the surfactant forms a self- assembled monolayer (SAM) on the surfaces of the nanoparticles.
  • the surfactant used is a peptide comprising an initial amino acid with a side thiol group (for example cysteine) which can bond semicovalently with gold.
  • the peptide is preferably formed of between 4 and 7 natural amino acids.
  • the vector according to the invention can be obtained by a click chemistry reaction between gold particles coated with a surfactant and an azide of the active agent.
  • the peptide has an alkyne side chain, preferably in a position adjacent to the terminal carboxyl.
  • the alkyne side chain is introduced into the peptide using a terminal amino acid such as propargyl glycine; however, the choice of amino acids forming the peptide, except for the characteristics mentioned above, is not binding, provided that hydrophobic side groups are present in the amino acids forming the centre part of the peptide, for example aromatic or alkyl groups.
  • Surfactant-coated colloidal gold is generally prepared by placing a colloidal solution of gold, which may include a salt solution (NaCl), in contact with stirring with a stirred solution of the surfactant, preferably at ambient temperature.
  • a colloidal solution of gold which may include a salt solution (NaCl)
  • NaCl salt solution
  • the alkyne-modified peptide Using the alkyne-modified peptide a stable gold colloid having two functional groups (subsequently AuNsG) with carboxylic acid and alkyne groups on the surface of the nanoparticles is obtained; as a result of its structural characteristics, the product obtained can be conjugated with several molecular species.
  • the alkyne groups can be easily coupled to any azide moiety using click chemistry reactions, obtaining the 1,2,3-triazole ring bonding between the metal nanostructures and the moiety (AuNsGFn).
  • the coated gold particles are caused to react with an active agent provided with a terminal azide group (-N 3 ); in one embodiment, the azide group may be bonded to the active agent through linkers having two functional groups (e.g. C 1 -C4) (which therefore have an azide functional group and an amine or carboxylic functional group at the opposite terminal portions of the alkyl chain).
  • the azide group may be bonded to the active agent through linkers having two functional groups (e.g. C 1 -C4) (which therefore have an azide functional group and an amine or carboxylic functional group at the opposite terminal portions of the alkyl chain).
  • the click chemistry reaction and the corresponding conditions for bioconjugation through the cycloaddition of copper (I)-catalysed azide-alkyne compounds are well known in the literature and described for example by Wang et al. in J. Am. Chem. Soc. 2003, 125, 3192- 3193 (which is intended to be incorporated herein following citation thereof).
  • the reaction uses copper catalysts, for example copper sulfate catalysts, in the presence of a reducing agent such as ascorbic acid; the reaction may be performed with stirring at ambient temperature, under physiological conditions, in times of between 3 and 24 hours.
  • reaction results in the acquisition of a vector according to the invention, in which the active agent is bound to the peptide through a triazole ring.
  • this terminal group comprises both compounds having therapeutic activity and compounds whose release in situ is desirable for diagnostic purposes.
  • drugs such as doxorubicin, daunorubicin, cisplatin, gemcitabine, citarabine, mitoxantrone hydrochloride, vincristine sulfate, vinblastine sulfate, bleomycin sulfate, irinotecan hydrochloride, topotecan hydrochloride, cefotiam, lamivudine, tetracycline hydrochloride, moxifloxacin hydrochloride, sodium methotrexate, paclitaxel, docetaxel, cyclosporine, rapamycin, olanzapine and simvastatin are included within the scope of active agents; active pharmaceutical agents having a peptide or protein structure may also be conjugated; therapeutically active agents having antitumoural activity are preferred.
  • the controlled release vector for the active agent so obtained can be kept for example in PBS (phosphate buffered saline) buffer at pH 7.3 or in borate solutions at pH 9.
  • PBS phosphate buffered saline
  • kits for example a two-component kit containing a composition of peptide-coated gold particles and separately an azidated active agent is envisaged for extemporaneous preparation of the vector.
  • Azidated active agents are commercially available.
  • Therapeutic or diagnostic use of the vector comprises its administration in therapeutically effective doses or in doses suitable for diagnostic purposes and the stage of non-invasive irradiation of the human body with laser light in the visible or near infrared (NIR) to cause release of the active agent in situ, in order to bring about photo-induced cleavage of the photolabile group (e.g. the triazole group).
  • NIR visible or near infrared
  • the invention provides a photorelease system or device capable of releasing its charge of active agent in living cells at wavelengths greater than 400 nm. Its operation is based on a multiple photon effect, encouraged by excitation of the localised surface plasmon (LSP) of the gold nanostructure very close to the 1,2,3-triazole rings.
  • LSP localised surface plasmon
  • This new application of the operating principle makes it possible to obtain photocleavage which, in spatio-temporal terms, is programmed in tenths of a second or less using a cw laser and a relatively low power, orders of magnitude lower than the peak power typically used for multiphoton microscopy with pulsed laser beams; for example, laser light having a wavelength of 561 nm with a power of the order of 30-300 ⁇ , preferably 100-280 ⁇ , is used within the scope of the invention.
  • the vector according to the invention can be used with a standard confocal microscopy set-up; for example, use of radiation at 561 nm offers considerable advantages in comparison with shorter wavelengths, such as greater tissue penetration and less cytotoxicity.
  • the possibility of obtaining two functional groups at right angles in the nanostructures makes it possible to produce complex multifunctional systems with nanosensors comprising both photocleavable loads and photostable targeting sequences.
  • the possibility of using other molecules which can be photocleaved using light of wavelength in the red such as o-nitrobenzylethers with a maximum absorption beyond 400 nm, or adding lanthanide crystals for their up-conversion properties, opens the way to controlled NIR photocleavage, with a very wide application in the sectors of nanomedicine and in vitro and in vivo administration/detection.
  • Figure 1A is a diagrammatical representation of the conjugation reaction through click chemistry and the photorelease reaction due to cleavage under irradiation at 561 nm; 1 indicates a gold particle, 2 the peptide structure (CLPFF-propargyl glycine in the example), 3 the conjugated active agent, fluorescein-azide in the example, and 4 the 1,2,3- triazole ring;
  • Figure IB is a graph illustrating, respectively:
  • Figures 2A and 2B are diagrams illustrating typical sample and control release graphs according to Example 5;
  • Figure 3 is a diagram demonstrating controlled release of fluorescein following the absorption of three photons of light at 561 nm, with reference to Example 5 below.
  • Hydrogen tetrachloroaurate (III) (HAuCl 4 ) trihydrate (99.99%) was obtained from Alfa Aesar, and all the other products were obtained from Sigma- Aldrich.
  • Seeds of gold were prepared by refluxing 100 ml of aqueous solution of HAuCl 4 (1 mM) with sodium acrylate (24 mM) for 30 minutes. The reaction produced a colloid with an intense red colour characteristic of 14 nm spheres.
  • the entire seed solution was mixed with 15 ml of a 25 mM HAuCl 4 solution and diluted in 845 ml of MilliQ water. After the mixture had been adjusted to pH 7, 40 ml of 0.5 M acrylic acid solution were added and in 3 days under continuous stirring at 22°C the reaction produced a colloidal solution of a wine-red colour comprising gold nanospheres (AuNs) of diameter 30 ⁇ 1.7 nm suspended in aqueous solution at a concentration of 0.5 nM (2.92 ⁇ 10 n Ns/ml), as deduced from the absorption spectra in the ultraviolet-visible (UV-Vis).
  • AuNs gold nanospheres
  • the spectra were measured using a Jasco 550 spectrophotometer (Jasco, Tokyo, Japan) fitted with a Jasco ETC-505T thermostat; the colloidal concentration was calculated using the known molar extinction coefficient.
  • the original solution of AuNs underwent three stages of washing with 40 mM borate solution at pH 9 using filters from an Amicon-15 100K centrifuge.
  • the nanospheres with two functional groups (AuNsG) were prepared by mixing 1 ml of a 1 mM stock solution of CLPFF-propargyl glycine peptide (G, Figure 1) in 1 mM NaCl with 9 ml of the abovementioned colloid at ambient temperature, with stirring for 90 minutes.
  • the encapsulated nanostructures obtained were purified from non-conjugate molecules by four stages of washing in 10 mM borate solution at pH 9 with Amicon-15 100K. Assuming that each peptide chain carries approximately 0.2 nm 2 of the surface area of the gold nanoparticles, the substitution process was carried out in the presence of a peptide excess of more than 100 times greater than the complete surface area available on the nanospheres to ensure rapid and complete surface coverage.
  • the pepti de-coated gold nanospheres were subjected to three stages of washing with a 150 mM PBS solution at pH 7.3 using Amicon-15 100K centrifuge filters.
  • the AuNsGFn system was prepared by mixing 1 ml of the AuNsG colloid with 14 ⁇ of 0.098 mM fluorescein-azide (Example 4) and 1 ⁇ of a fresh solution of 10 mM copper sulfate and 50 mM ascorbic acid, stirring for 3 hours at ambient temperature.
  • the conjugated nanostructures obtained were purified from the unreacted molecules by four stages of washing in a 10 mM borate solution at pH 9 with Amicon-15 100K and held at 4°C for a maximum of 1 hour prior to use.
  • 5 (6)-carboxy fluorescein amido-ethylazide 5 (6)-caraboxyfluorescein (50 mg, 0.13 mmoles) was dissolved in 1 ml of dry DMSO. Dicyclohexylcarbodiimide (0.13 mmoles), NHS (0.13 mmoles), azidoethylamine (11 mg, 0.13 mmoles) and Et 3 N (0.26 mmoles) were added and the mixture was stirred at 25°C.
  • human osteosarcoma cell lines (U20S cells) were incubated with AuNsGFn.
  • Fluorescein was selected as the example active principle/sensor to check its release through measuring fluorescence.
  • Gold nanoparticles are suppressors of fluorescence (quenchers); this characteristic therefore makes it possible to trace the photorelease of the sensors by monitoring the increase in fluorescence intensity following the light stimulus.
  • the cells were incubated with a solution of nanostructures (20 pM) in PBS for 20 minutes at 37°C and revealed one hour after removal of the non-internalised colloid by rinsing with fresh cellular medium.
  • the vitality of the cells which had incorporated the photocleavable systems was checked using the trypan blue test and the propidium iodide test.
  • Confocal fluorescence microscopy images of these cells were obtained by exciting the sample with laser light of 488 nm of a power below - 35 ⁇ to reduce the phenomenon of photodestruction of the fluorescein released to a minimum. Living cells were also irradiated with laser beams at 561 nm for specified periods.
  • Confocal fluorescence microscopy images show that a signal which can be detected in the fluorescein channel is recorded only after a pulse at 561 nm. The fluorescence is diffuse within the cells, consistent with the photorelease of fluorescein by internalised AuNsGFn systems and diffusion of the fluorescein within the cell.
  • a non-cleavable system in which fluorescein-cadaverine (F) was conjugated with the nanospheres coated with peptide by means of a photostable amide linker through chemical reactions of the EDC NHS type was synthesised as a control.
  • Fluorescein release only occurs when the nanoparticles are in the focal plane. In fact, when the latter passes through the volume of the cell, the fluorescein bound to the gold nanoparticles is released (and greater fluorescence is recorded), with an observed time horizon of tens of seconds ( Figure 2A).
  • z-stacks of the entire cell volume were performed with each z scan lasting approximately 100 seconds for a line scanning frequency of 400 Hz.
  • images of the sample irradiated with laser at 488 nm were obtained.
  • FIG. 3 shows the integrated fluorescence within a cell in a typical experiment as a function of the integral over time of the cube of the power. Passes along the X axis are proportional to the cube of the power of the laser at 561 nm used during the z-stacfa, multiplied by the irradiation time.
  • Figure IB shows the calculated absorption spectrum of 1,2,3-triazole (for one photon). The latter shows a band at 190-220 nm, without any absorption at wavelengths greater than 220 nm. However at ⁇ 560 nm the ⁇ 3 ⁇ is of the same order of magnitude as envisaged for the other organic molecule peaks ( ⁇ 10 "80 cmVph "2 ).
  • this transverse 3 -photon absorption cross section is greatly increased (a factor of the order of ⁇ 10 12 ), and results in a system excitation level compatible with the experimental observations.
  • Other photorelease mechanisms relating to other parts of the coating are ruled out on the basis of the absence of photorelease in the non-cleavable control system, which differs only in the fact that the linker through the triazole ring is replaced by an amide linker.
  • the power values of the 561 nm laser used in this work vary between 30 ⁇ and 280 ⁇ , well below the intensities commonly used to promote photothermal effects. The latter are known to be very much more significant in the case of gold nanospheres having smaller diameters ( ⁇ 15 nm).
  • the high thermal stability of the triazole ring (up to 500°C) ensures that cleavage is not induced thermally.
  • fluorescein in the above examples is purely for the purposes of experimentally verifying the function of the vector and that other active agents, as indicated previously, can be conjugated to the nanostructures and therefore released with good spatio-temporal control.
  • coating peptides having structural characteristics other than those used in the specific embodiments above can be used provided that they meet the requirements specified in the following claims.

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Abstract

L'invention concerne un vecteur pour la libération spatialement et temporairement contrôlée d'un composant actif comprenant des nanoparticules d'or revêtues d'un agent tensioactif et un composant actif lié audit agent tensioactif au moyen d'une liaison photoclivable, ledit vecteur étant apte à libérer le composant actif lorsqu'il est exposé à un rayonnement lumineux de longueur d'onde supérieure à 400 nm inclus dans la région du visible ou dans la région du proche infrarouge (NIR) par un effet à photons multiples. L'invention concerne, en particulier, un vecteur dans lequel le groupe ayant une liaison photolabile est 1,2,3-triazole, qui peut par exemple être obtenu par une réaction de chimie clic entre des particules d'or sur la surface desquelles des molécules peptides ayant un groupe terminal carboxyle libre et un groupe de côté alcyne sont chimiadsorbés et un azide du composant actif.
PCT/IB2012/053220 2011-06-27 2012-06-26 Vecteur pour la libération d'un composant actif qui est photoclivable par irradiation dans le visible Ceased WO2013001451A1 (fr)

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IT000561A ITTO20110561A1 (it) 2011-06-27 2011-06-27 Vettore per il rilascio di un agente attivo, fotoscindibile per irraggiamento nel visibile
ITTO2011A000561 2011-06-27

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015099624A1 (fr) * 2013-12-26 2015-07-02 Yavuz Mustafa Selman Nanostructures recouvertes d'espèces présentant des lieurs clivables photothermiquement pour l'administration contrôlée d'une charge

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008127743A2 (fr) * 2007-01-05 2008-10-23 William Marsh Rice University Composition utilisée pour l'administration et la libération contrôlée de médicament cible
WO2010046377A2 (fr) * 2008-10-23 2010-04-29 Fundació Privada Institut Català De Nanotecnologia Conjugués immuno-activateurs comprenant des nanoparticules revêtues de peptides
US20100233224A1 (en) 2009-02-23 2010-09-16 Epir Technologies, Inc. Photolytic release of biocides for high efficiency decontamination through phospholipid nanoparticles
WO2010104819A2 (fr) 2009-03-09 2010-09-16 Board Of Regents, The University Of Texas System Nanosphères d'or creuses (hauns) et microsphères chargées en hauns utiles dans l'administration de médicaments
WO2011070333A2 (fr) * 2009-12-10 2011-06-16 Trillion Genomics Limited Sondes

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008127743A2 (fr) * 2007-01-05 2008-10-23 William Marsh Rice University Composition utilisée pour l'administration et la libération contrôlée de médicament cible
WO2010046377A2 (fr) * 2008-10-23 2010-04-29 Fundació Privada Institut Català De Nanotecnologia Conjugués immuno-activateurs comprenant des nanoparticules revêtues de peptides
US20100233224A1 (en) 2009-02-23 2010-09-16 Epir Technologies, Inc. Photolytic release of biocides for high efficiency decontamination through phospholipid nanoparticles
WO2010104819A2 (fr) 2009-03-09 2010-09-16 Board Of Regents, The University Of Texas System Nanosphères d'or creuses (hauns) et microsphères chargées en hauns utiles dans l'administration de médicaments
WO2011070333A2 (fr) * 2009-12-10 2011-06-16 Trillion Genomics Limited Sondes

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
GANG HAN ET AL.: "Light-regulated DNA transcription and delivery using photolabilegold nanoparticles", ABSTRACTS OF PAPERS, 231ST ACS NATIONAL MEETING, ATLANTA,GA, UNITED STATES, MARCH 26-30, 2006 (2006), 1 April 2006 (2006-04-01), XP008145405 *
JUN NAKANISHI ET AL: "Light-Regulated Activation of Cellular Signaling by Gold Nanoparticles That Capture and Release Amines", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 131, no. 11, 25 March 2009 (2009-03-25), pages 3822 - 3823, XP055012539, ISSN: 0002-7863, DOI: 10.1021/ja809236a *
SARIT S. AGASTI ET AL: "Photoregulated Release of Caged Anticancer Drugs from Gold Nanoparticles", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 131, no. 16, 29 April 2009 (2009-04-29), pages 5728 - 5729, XP055012506, ISSN: 0002-7863, DOI: 10.1021/ja900591t *
WANG ET AL., J. AM. CHEM. SOC., vol. 125, 2003, pages 3192 - 3193

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015099624A1 (fr) * 2013-12-26 2015-07-02 Yavuz Mustafa Selman Nanostructures recouvertes d'espèces présentant des lieurs clivables photothermiquement pour l'administration contrôlée d'une charge

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