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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

Impact of nanoparticles-containing photosensitizer and peptide (NP-TPC-ATWLPPR) or nanoparticles only (NP) on MDA-MB-231 cell activities in darkness. A) MDA-MB-231 cells were exposed to NP-TPC-ATWLPPR (black) or NP (gray) at the indicated concentrations for 24 h at 37°C. Cells were washed and incubated at 37°C for further 24 h. Cell viability was then measured using MTT test (values are presented as the mean ± S.D). B) Kinetics of the normalized cell index of the MDA-MB-231 cells exposed to various concentrations of NP-TPC-ATWLPPR (a) or the corresponding concentrations of gadolinium in the control NP (b) for 24h before washing. Cell index was monitored during 143 h after nanoparticles exposure by using the xCELLigence system. All reported data are the means of six replicates.
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Figure 3: Impact of nanoparticles-containing photosensitizer and peptide (NP-TPC-ATWLPPR) or nanoparticles only (NP) on MDA-MB-231 cell activities in darkness. A) MDA-MB-231 cells were exposed to NP-TPC-ATWLPPR (black) or NP (gray) at the indicated concentrations for 24 h at 37°C. Cells were washed and incubated at 37°C for further 24 h. Cell viability was then measured using MTT test (values are presented as the mean ± S.D). B) Kinetics of the normalized cell index of the MDA-MB-231 cells exposed to various concentrations of NP-TPC-ATWLPPR (a) or the corresponding concentrations of gadolinium in the control NP (b) for 24h before washing. Cell index was monitored during 143 h after nanoparticles exposure by using the xCELLigence system. All reported data are the means of six replicates.

Mentions: Dark cytotoxicity (without light irradiation) was first assessed by MTT test on the MDA-MB-231 breast cancer cells, overexpressing NRP-1 receptor 38. Increasing concentrations of nanoparticles-grafted photosensitizer molecules (NP-TPC-ATWLPPR) or photosensitizer-free nanoparticles (NP) (from 0.05 to 10.00 µM of TPC, corresponding to 2.9 to 585.0 µM of gadolinium oxide, respectively) were tested (Fig. 3). As shown on Figure 3A, 48 h after nanoparticles exposure, cytotoxic effect was evidenced only with the higher concentration (10.00 µM/585.0 µM) leading to a reduction of 37% and 41% of cell survival for NP-TPC-ATWLPPR and NP, respectively. No cytotoxic effect was measured (mean cell viability superior to 80%) for cells exposed with concentrations from 0.05 to 1.00 µM for both nanoparticle groups (NP-TPC-ATWLPPR and NP) compared to untreated cells (Fig. 3A).


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)

Impact of nanoparticles-containing photosensitizer and peptide (NP-TPC-ATWLPPR) or nanoparticles only (NP) on MDA-MB-231 cell activities in darkness. A) MDA-MB-231 cells were exposed to NP-TPC-ATWLPPR (black) or NP (gray) at the indicated concentrations for 24 h at 37°C. Cells were washed and incubated at 37°C for further 24 h. Cell viability was then measured using MTT test (values are presented as the mean ± S.D). B) Kinetics of the normalized cell index of the MDA-MB-231 cells exposed to various concentrations of NP-TPC-ATWLPPR (a) or the corresponding concentrations of gadolinium in the control NP (b) for 24h before washing. Cell index was monitored during 143 h after nanoparticles exposure by using the xCELLigence system. All reported data are the means of six replicates.
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Related In: Results  -  Collection

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Figure 3: Impact of nanoparticles-containing photosensitizer and peptide (NP-TPC-ATWLPPR) or nanoparticles only (NP) on MDA-MB-231 cell activities in darkness. A) MDA-MB-231 cells were exposed to NP-TPC-ATWLPPR (black) or NP (gray) at the indicated concentrations for 24 h at 37°C. Cells were washed and incubated at 37°C for further 24 h. Cell viability was then measured using MTT test (values are presented as the mean ± S.D). B) Kinetics of the normalized cell index of the MDA-MB-231 cells exposed to various concentrations of NP-TPC-ATWLPPR (a) or the corresponding concentrations of gadolinium in the control NP (b) for 24h before washing. Cell index was monitored during 143 h after nanoparticles exposure by using the xCELLigence system. All reported data are the means of six replicates.
Mentions: Dark cytotoxicity (without light irradiation) was first assessed by MTT test on the MDA-MB-231 breast cancer cells, overexpressing NRP-1 receptor 38. Increasing concentrations of nanoparticles-grafted photosensitizer molecules (NP-TPC-ATWLPPR) or photosensitizer-free nanoparticles (NP) (from 0.05 to 10.00 µM of TPC, corresponding to 2.9 to 585.0 µM of gadolinium oxide, respectively) were tested (Fig. 3). As shown on Figure 3A, 48 h after nanoparticles exposure, cytotoxic effect was evidenced only with the higher concentration (10.00 µM/585.0 µM) leading to a reduction of 37% and 41% of cell survival for NP-TPC-ATWLPPR and NP, respectively. No cytotoxic effect was measured (mean cell viability superior to 80%) for cells exposed with concentrations from 0.05 to 1.00 µM for both nanoparticle groups (NP-TPC-ATWLPPR and NP) compared to untreated cells (Fig. 3A).

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