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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

In vitro photodynamic activity of nanoparticles-containing photosensitizer and peptide (NP-TPC-ATWLPPR) according to MTT assay. MDA-MB-231 cells were exposed to 0.1 µM (black) and 1.0 µM (gray) of TPC in NP-TPC-ATWLPPR. Following a 24 h-incubation at 37°C, cells were washed and exposed to the indicated doses of light and incubated for further 24 h. Cell viability was then measured using MTT assay. Values are the average of six replicates and presented as the mean ± S.D. DL50 = 9.2 or 2.8 J/cm2 at 0.1 and 1 µM of TPC in NP-TPC-ATWLPPR, respectively.
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Figure 4: In vitro photodynamic activity of nanoparticles-containing photosensitizer and peptide (NP-TPC-ATWLPPR) according to MTT assay. MDA-MB-231 cells were exposed to 0.1 µM (black) and 1.0 µM (gray) of TPC in NP-TPC-ATWLPPR. Following a 24 h-incubation at 37°C, cells were washed and exposed to the indicated doses of light and incubated for further 24 h. Cell viability was then measured using MTT assay. Values are the average of six replicates and presented as the mean ± S.D. DL50 = 9.2 or 2.8 J/cm2 at 0.1 and 1 µM of TPC in NP-TPC-ATWLPPR, respectively.

Mentions: On the basis of the data obtained from the dark cytotoxicity studies using MTT test (Fig. 3A), photodynamic activity was investigated with two non cytotoxic concentrations of TPC (0.1 and 1.0 µM) into the nanoparticles NP-TPC-ATWLPPR. MDA-MB-231 cancer cells were exposed to 0.1 and 1.0 µM of TPC into NP-TPC-ATWLPPR for 24 h. Following washing, the cells were irradiated with various doses of red light (652 nm). After 24 h post-irradiation, cell viability was estimated with MTT test. As shown in figure 4, the nanoparticles induced a light dose-dependent increase in photocytotoxicity, achieving at 20 J/cm2 a decrease in cell viability up to 24 and 1% for 0.1 and 1.0 µM TPC, respectively. Moreover, the nanoparticles exhibited photocytotoxicity in a TPC concentration-dependent manner as the nanoparticles at 1.0 µM was 3.3 times more effective than 0.1 µM (50% cell growth inhibitory light dose, DL50 = 9.16 vs. 2.80 J/cm2 at 0.1 and 1.0 µM, respectively).


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)

In vitro photodynamic activity of nanoparticles-containing photosensitizer and peptide (NP-TPC-ATWLPPR) according to MTT assay. MDA-MB-231 cells were exposed to 0.1 µM (black) and 1.0 µM (gray) of TPC in NP-TPC-ATWLPPR. Following a 24 h-incubation at 37°C, cells were washed and exposed to the indicated doses of light and incubated for further 24 h. Cell viability was then measured using MTT assay. Values are the average of six replicates and presented as the mean ± S.D. DL50 = 9.2 or 2.8 J/cm2 at 0.1 and 1 µM of TPC in NP-TPC-ATWLPPR, respectively.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3475218&req=5

Figure 4: In vitro photodynamic activity of nanoparticles-containing photosensitizer and peptide (NP-TPC-ATWLPPR) according to MTT assay. MDA-MB-231 cells were exposed to 0.1 µM (black) and 1.0 µM (gray) of TPC in NP-TPC-ATWLPPR. Following a 24 h-incubation at 37°C, cells were washed and exposed to the indicated doses of light and incubated for further 24 h. Cell viability was then measured using MTT assay. Values are the average of six replicates and presented as the mean ± S.D. DL50 = 9.2 or 2.8 J/cm2 at 0.1 and 1 µM of TPC in NP-TPC-ATWLPPR, respectively.
Mentions: On the basis of the data obtained from the dark cytotoxicity studies using MTT test (Fig. 3A), photodynamic activity was investigated with two non cytotoxic concentrations of TPC (0.1 and 1.0 µM) into the nanoparticles NP-TPC-ATWLPPR. MDA-MB-231 cancer cells were exposed to 0.1 and 1.0 µM of TPC into NP-TPC-ATWLPPR for 24 h. Following washing, the cells were irradiated with various doses of red light (652 nm). After 24 h post-irradiation, cell viability was estimated with MTT test. As shown in figure 4, the nanoparticles induced a light dose-dependent increase in photocytotoxicity, achieving at 20 J/cm2 a decrease in cell viability up to 24 and 1% for 0.1 and 1.0 µM TPC, respectively. Moreover, the nanoparticles exhibited photocytotoxicity in a TPC concentration-dependent manner as the nanoparticles at 1.0 µM was 3.3 times more effective than 0.1 µM (50% cell growth inhibitory light dose, DL50 = 9.16 vs. 2.80 J/cm2 at 0.1 and 1.0 µM, respectively).

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