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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.

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Cerebral biodistribution and tumor MRI contrast enhancement by gadolinium-based hybrid silica nanoparticles with or without targeting peptide monitored during 1h and, immediately after intravenous injection. Dynamic T1-weighted images acquisition was started before intravenous injection of the nanoparticles (25 µmol of Gd / 250 g of body weight) to characterize the kinetics of the nanoparticles biodistribution in the tumor. MRI signal intensity kinetics of injected peptide-conjugated NP-TPC-ATWLPPR (A), and un-conjugated NP (B) nanoparticles were expressed as the enhancement of contrast (EHC %) normalized on pre-injection signal. The curves represent time-dependent signal intensity recorded from different ROIs selected from:  Controlateral healthy hemisphere, Tumor tissue, or  the EHC in the tumor tissue as normalized on the contolateral healthy hemisphere. C) T1 coronal MRI images obtained (1) before nanoparticles injection, (2) maximal MRI signal intensity after injection and (3) 1h post-injection.
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Figure 6: Cerebral biodistribution and tumor MRI contrast enhancement by gadolinium-based hybrid silica nanoparticles with or without targeting peptide monitored during 1h and, immediately after intravenous injection. Dynamic T1-weighted images acquisition was started before intravenous injection of the nanoparticles (25 µmol of Gd / 250 g of body weight) to characterize the kinetics of the nanoparticles biodistribution in the tumor. MRI signal intensity kinetics of injected peptide-conjugated NP-TPC-ATWLPPR (A), and un-conjugated NP (B) nanoparticles were expressed as the enhancement of contrast (EHC %) normalized on pre-injection signal. The curves represent time-dependent signal intensity recorded from different ROIs selected from: Controlateral healthy hemisphere, Tumor tissue, or the EHC in the tumor tissue as normalized on the contolateral healthy hemisphere. C) T1 coronal MRI images obtained (1) before nanoparticles injection, (2) maximal MRI signal intensity after injection and (3) 1h post-injection.

Mentions: To investigate MRI contrast enhancement in tumor tissue, cerebral MRI analysis of nude rats with orthotopic U87 glioblastoma model was performed about 20 days after intracranial tumor implantation. MRI analysis of the tumor tissue was investigated for intravenously injected un-conjugated and peptide-targeted gadolinium-based hybrid nanoparticles. Dynamic data of MRI signal intensity from the selected regions of interest (ROIs) in the tumor and the controlateral tissue were expressed as the mean signal per area unit and used to create kinetics of MRI contrast enhancement (EHC %) for all time points post-injection. The kinetics represent MRI contrast enhancement in both tumor and controlateral tissue normalized to the pre-injection MRI signal, and MRI contrast enhancement in tumor tissue normalized to controlateral tissue (Fig. 6A-B). As shown in Fig. 6A-B, immediately after intravenous injection, whatever the nanoparticles types the MRI contrast enhancement increased rapidly and specifically in tumor ROIs to achieve maximum enhancement at 2-7 min post-injection, reflecting nanoparticles incorporation in tumor. We can note that tumor MRI signal intensity appears to be higher in rats injected with non-targeted nanoparticles probably due to higher pre-injection MRI signal (2.5-fold) because of more extended tumor mass as compared to that injected with targeted nanoparticles (Fig. 6B-C).


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)

Cerebral biodistribution and tumor MRI contrast enhancement by gadolinium-based hybrid silica nanoparticles with or without targeting peptide monitored during 1h and, immediately after intravenous injection. Dynamic T1-weighted images acquisition was started before intravenous injection of the nanoparticles (25 µmol of Gd / 250 g of body weight) to characterize the kinetics of the nanoparticles biodistribution in the tumor. MRI signal intensity kinetics of injected peptide-conjugated NP-TPC-ATWLPPR (A), and un-conjugated NP (B) nanoparticles were expressed as the enhancement of contrast (EHC %) normalized on pre-injection signal. The curves represent time-dependent signal intensity recorded from different ROIs selected from:  Controlateral healthy hemisphere, Tumor tissue, or  the EHC in the tumor tissue as normalized on the contolateral healthy hemisphere. C) T1 coronal MRI images obtained (1) before nanoparticles injection, (2) maximal MRI signal intensity after injection and (3) 1h post-injection.
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Related In: Results  -  Collection

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Figure 6: Cerebral biodistribution and tumor MRI contrast enhancement by gadolinium-based hybrid silica nanoparticles with or without targeting peptide monitored during 1h and, immediately after intravenous injection. Dynamic T1-weighted images acquisition was started before intravenous injection of the nanoparticles (25 µmol of Gd / 250 g of body weight) to characterize the kinetics of the nanoparticles biodistribution in the tumor. MRI signal intensity kinetics of injected peptide-conjugated NP-TPC-ATWLPPR (A), and un-conjugated NP (B) nanoparticles were expressed as the enhancement of contrast (EHC %) normalized on pre-injection signal. The curves represent time-dependent signal intensity recorded from different ROIs selected from: Controlateral healthy hemisphere, Tumor tissue, or the EHC in the tumor tissue as normalized on the contolateral healthy hemisphere. C) T1 coronal MRI images obtained (1) before nanoparticles injection, (2) maximal MRI signal intensity after injection and (3) 1h post-injection.
Mentions: To investigate MRI contrast enhancement in tumor tissue, cerebral MRI analysis of nude rats with orthotopic U87 glioblastoma model was performed about 20 days after intracranial tumor implantation. MRI analysis of the tumor tissue was investigated for intravenously injected un-conjugated and peptide-targeted gadolinium-based hybrid nanoparticles. Dynamic data of MRI signal intensity from the selected regions of interest (ROIs) in the tumor and the controlateral tissue were expressed as the mean signal per area unit and used to create kinetics of MRI contrast enhancement (EHC %) for all time points post-injection. The kinetics represent MRI contrast enhancement in both tumor and controlateral tissue normalized to the pre-injection MRI signal, and MRI contrast enhancement in tumor tissue normalized to controlateral tissue (Fig. 6A-B). As shown in Fig. 6A-B, immediately after intravenous injection, whatever the nanoparticles types the MRI contrast enhancement increased rapidly and specifically in tumor ROIs to achieve maximum enhancement at 2-7 min post-injection, reflecting nanoparticles incorporation in tumor. We can note that tumor MRI signal intensity appears to be higher in rats injected with non-targeted nanoparticles probably due to higher pre-injection MRI signal (2.5-fold) because of more extended tumor mass as compared to that injected with targeted nanoparticles (Fig. 6B-C).

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