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Multifunctional Peptide-conjugated hybrid silica nanoparticles for photodynamic therapy and MRI.

Benachour H, Sève A, Bastogne T, Frochot C, Vanderesse R, Jasniewski J, Miladi I, Billotey C, Tillement O, Lux F, Barberi-Heyob M - Theranostics (2012)

Bottom Line: In vitro investigations demonstrated the ability of multifunctional nanoparticles to preserve the photophysical properties of the encapsulated photosensitizer and to confer photosensitivity to MDA-MB-231 cancer cells related to photosensitizer concentration and light dose.Using binding test, we revealed the ability of peptide-functionalized nanoparticles to target NRP-1 recombinant protein.Real-time MRI analysis revealed the ability of the targeting peptide to confer specific intratumoral retention of the multifunctional nanoparticles.

View Article: PubMed Central - PubMed

Affiliation: 1. Université de Lorraine, CRAN, UMR 7039, Campus Sciences, BP 70239, Vandœuvre-lès-Nancy Cedex, 54506, France ; 2. CNRS, CRAN, UMR 7039, France.

ABSTRACT
Photodynamic therapy (PDT) is an emerging theranostic modality for various cancer as well as non-cancer diseases. Its efficiency is mainly based on a selective accumulation of PDT and imaging agents in tumor tissue. The vascular effect is widely accepted to play a major role in tumor eradication by PDT. To promote this vascular effect, we previously demonstrated the interest of using an active- targeting strategy targeting neuropilin-1 (NRP-1), mainly over-expressed by tumor angiogenic vessels. For an integrated vascular-targeted PDT with magnetic resonance imaging (MRI) of cancer, we developed multifunctional gadolinium-based nanoparticles consisting of a surface-localized tumor vasculature targeting NRP-1 peptide and polysiloxane nanoparticles with gadolinium chelated by DOTA derivatives on the surface and a chlorin as photosensitizer. The nanoparticles were surface-functionalized with hydrophilic DOTA chelates and also used as a scaffold for the targeting peptide grafting. In vitro investigations demonstrated the ability of multifunctional nanoparticles to preserve the photophysical properties of the encapsulated photosensitizer and to confer photosensitivity to MDA-MB-231 cancer cells related to photosensitizer concentration and light dose. Using binding test, we revealed the ability of peptide-functionalized nanoparticles to target NRP-1 recombinant protein. Importantly, after intravenous injection of the multifunctional nanoparticles in rats bearing intracranial U87 glioblastoma, a positive MRI contrast enhancement was specifically observed in tumor tissue. Real-time MRI analysis revealed the ability of the targeting peptide to confer specific intratumoral retention of the multifunctional nanoparticles.

No MeSH data available.


Related in: MedlinePlus

Binding of ATWLPPR-targeted (NP-TPC-ATWLPPR) and untargeted (NP) nanoparticles to NRP-1 recombinant protein. Binding of the biotinylated VEGF (5 ng/mL) to recombinant chimeric NRP-1 protein, in the presence of 2 µg/mL heparin, was evaluated in competition with an excess of VEGF165 as positive control (0.5 µg/mL), NP-TPC-ATWLPPR (grey) or NP control (black) at the indicated concentrations of ATWLPPR or the corresponding concentrations of gadolinium (Gd), respectively. Data points show the mean ± S.D., n=3. EC50 = 56.6 µM (NP-TPC-ATWLPPR)
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Figure 2: Binding of ATWLPPR-targeted (NP-TPC-ATWLPPR) and untargeted (NP) nanoparticles to NRP-1 recombinant protein. Binding of the biotinylated VEGF (5 ng/mL) to recombinant chimeric NRP-1 protein, in the presence of 2 µg/mL heparin, was evaluated in competition with an excess of VEGF165 as positive control (0.5 µg/mL), NP-TPC-ATWLPPR (grey) or NP control (black) at the indicated concentrations of ATWLPPR or the corresponding concentrations of gadolinium (Gd), respectively. Data points show the mean ± S.D., n=3. EC50 = 56.6 µM (NP-TPC-ATWLPPR)

Mentions: The endothelium-homing peptide ATWLPPR was described to selectively target NRP-1 receptor expressed in angiogenic vasculature 19, 20, 22. The molecular affinity of the nanoparticles for recombinant NRP-1 protein was evaluated using competitive binding test. Increasing concentrations of peptide conjugated to NP-TPC-ATWLPPR nanoparticles or the corresponding concentrations of gadolinium in the control NP were tested. Results of binding test were presented in Fig. 2. Biotinylated VEGF165 bound to NRP-1 was greatly displaced by the peptide-conjugated nanoparticles NP-TPC-ATWLPPR, indicating that the conjugated nanoparticles bound to recombinant NRP-1 chimeric protein. Although slight interaction of the un-conjugated NP was only detected with the higher concentration tested, ATWLPPR-conjugated nanoparticles showed a peptide concentration-dependent binding to recombinant NRP-1 protein (EC50 = 56.6 µM for NP-TPC-ATWLPPR, corresponding to the concentration of competitor that displaced 50% of VEGF165 binding).


Multifunctional Peptide-conjugated hybrid silica nanoparticles for photodynamic therapy and MRI.

Benachour H, Sève A, Bastogne T, Frochot C, Vanderesse R, Jasniewski J, Miladi I, Billotey C, Tillement O, Lux F, Barberi-Heyob M - Theranostics (2012)

Binding of ATWLPPR-targeted (NP-TPC-ATWLPPR) and untargeted (NP) nanoparticles to NRP-1 recombinant protein. Binding of the biotinylated VEGF (5 ng/mL) to recombinant chimeric NRP-1 protein, in the presence of 2 µg/mL heparin, was evaluated in competition with an excess of VEGF165 as positive control (0.5 µg/mL), NP-TPC-ATWLPPR (grey) or NP control (black) at the indicated concentrations of ATWLPPR or the corresponding concentrations of gadolinium (Gd), respectively. Data points show the mean ± S.D., n=3. EC50 = 56.6 µM (NP-TPC-ATWLPPR)
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3475218&req=5

Figure 2: Binding of ATWLPPR-targeted (NP-TPC-ATWLPPR) and untargeted (NP) nanoparticles to NRP-1 recombinant protein. Binding of the biotinylated VEGF (5 ng/mL) to recombinant chimeric NRP-1 protein, in the presence of 2 µg/mL heparin, was evaluated in competition with an excess of VEGF165 as positive control (0.5 µg/mL), NP-TPC-ATWLPPR (grey) or NP control (black) at the indicated concentrations of ATWLPPR or the corresponding concentrations of gadolinium (Gd), respectively. Data points show the mean ± S.D., n=3. EC50 = 56.6 µM (NP-TPC-ATWLPPR)
Mentions: The endothelium-homing peptide ATWLPPR was described to selectively target NRP-1 receptor expressed in angiogenic vasculature 19, 20, 22. The molecular affinity of the nanoparticles for recombinant NRP-1 protein was evaluated using competitive binding test. Increasing concentrations of peptide conjugated to NP-TPC-ATWLPPR nanoparticles or the corresponding concentrations of gadolinium in the control NP were tested. Results of binding test were presented in Fig. 2. Biotinylated VEGF165 bound to NRP-1 was greatly displaced by the peptide-conjugated nanoparticles NP-TPC-ATWLPPR, indicating that the conjugated nanoparticles bound to recombinant NRP-1 chimeric protein. Although slight interaction of the un-conjugated NP was only detected with the higher concentration tested, ATWLPPR-conjugated nanoparticles showed a peptide concentration-dependent binding to recombinant NRP-1 protein (EC50 = 56.6 µM for NP-TPC-ATWLPPR, corresponding to the concentration of competitor that displaced 50% of VEGF165 binding).

Bottom Line: In vitro investigations demonstrated the ability of multifunctional nanoparticles to preserve the photophysical properties of the encapsulated photosensitizer and to confer photosensitivity to MDA-MB-231 cancer cells related to photosensitizer concentration and light dose.Using binding test, we revealed the ability of peptide-functionalized nanoparticles to target NRP-1 recombinant protein.Real-time MRI analysis revealed the ability of the targeting peptide to confer specific intratumoral retention of the multifunctional nanoparticles.

View Article: PubMed Central - PubMed

Affiliation: 1. Université de Lorraine, CRAN, UMR 7039, Campus Sciences, BP 70239, Vandœuvre-lès-Nancy Cedex, 54506, France ; 2. CNRS, CRAN, UMR 7039, France.

ABSTRACT
Photodynamic therapy (PDT) is an emerging theranostic modality for various cancer as well as non-cancer diseases. Its efficiency is mainly based on a selective accumulation of PDT and imaging agents in tumor tissue. The vascular effect is widely accepted to play a major role in tumor eradication by PDT. To promote this vascular effect, we previously demonstrated the interest of using an active- targeting strategy targeting neuropilin-1 (NRP-1), mainly over-expressed by tumor angiogenic vessels. For an integrated vascular-targeted PDT with magnetic resonance imaging (MRI) of cancer, we developed multifunctional gadolinium-based nanoparticles consisting of a surface-localized tumor vasculature targeting NRP-1 peptide and polysiloxane nanoparticles with gadolinium chelated by DOTA derivatives on the surface and a chlorin as photosensitizer. The nanoparticles were surface-functionalized with hydrophilic DOTA chelates and also used as a scaffold for the targeting peptide grafting. In vitro investigations demonstrated the ability of multifunctional nanoparticles to preserve the photophysical properties of the encapsulated photosensitizer and to confer photosensitivity to MDA-MB-231 cancer cells related to photosensitizer concentration and light dose. Using binding test, we revealed the ability of peptide-functionalized nanoparticles to target NRP-1 recombinant protein. Importantly, after intravenous injection of the multifunctional nanoparticles in rats bearing intracranial U87 glioblastoma, a positive MRI contrast enhancement was specifically observed in tumor tissue. Real-time MRI analysis revealed the ability of the targeting peptide to confer specific intratumoral retention of the multifunctional nanoparticles.

No MeSH data available.


Related in: MedlinePlus