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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

Absorption spectra, size and zeta potential of gadolinium-based hybrid silica nanoparticles. (A) Size distribution by volume of the hydrodynamic diameter (expressed in nm) of nanoparticles (NP-TPC-ATWLPPR or NP) in suspension at 20°C. (B) Zeta potential distribution (expressed in mV) of the nanoparticles (NP-TPC-ATWLPPR or NP) suspensions. (C) Absorption spectra of free photosensitizer TPC and suspension of NP-TPC-ATWLPPR nanoparticles in ethanol.
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Figure 1: Absorption spectra, size and zeta potential of gadolinium-based hybrid silica nanoparticles. (A) Size distribution by volume of the hydrodynamic diameter (expressed in nm) of nanoparticles (NP-TPC-ATWLPPR or NP) in suspension at 20°C. (B) Zeta potential distribution (expressed in mV) of the nanoparticles (NP-TPC-ATWLPPR or NP) suspensions. (C) Absorption spectra of free photosensitizer TPC and suspension of NP-TPC-ATWLPPR nanoparticles in ethanol.

Mentions: Size distribution and Zeta potential of the nanoparticles were presented in Fig. 1A and B, respectively, and values were summarized in Table 1. Hydrodynamic diameter was 4.6 and 3.3 nm for NP-TPC-ATLLPPR and NP, respectively. Hence, one can observe that peptide grafting on the surface of nanoparticles (~ 3 peptides per nanoparticle) and TPC encapsulating into the silica shell (~1.7 TPC molecules per nanoparticle) induce only slight increase in the hydrodynamic diameter (4.6 vs. 3.3 nm for NP-TPC-ATWLPPR and NP, respectively). The two nanoparticles batches were characterized by a single narrow peak with around 99.5% of the size distribution by volume (Fig. 1A). This indicates that the nanoparticles were monodisperse in water probably because of their derivatization by the DOTA polymers. Zeta potentials were also determined in ultrapure water to avoid the presence of counterions which could neutralize the charges on the nanoparticles. Positive charge of 12.9 ± 4.0 and 4.3 ± 3.5 mV was measured for NP-TPC-ATWLPPR and NP, respectively (Fig. 1B and Table 1). As suggested by our group 34, the higher positive charge of the peptide-conjugated nanoparticles (12.9±4.0 mV) may be brought by the surface-grafted peptide ATWLPPR (~ 3 peptides per nanoparticle). UV/Vis spectra of the NP-TPC-ATWLPPR nanoparticles showed that the nanoparticles displayed similar absorption features to free TPC, with the Soret-band and the respective Q-bands (Fig. 1C). No shift of the maximum absorption at Soret-band can be observed, suggesting that the photosensitizer was mainly in a monomeric form without aggregation inside the nanoparticles. This indicates that the photophysical properties of TPC molecules in the nanoparticles were well retained. According to the calibration curve of the UV/Vis absorption spectra of free TPC, the amount of grafted TPC within the nanoparticles NP-TPC-ATWLPPR was estimated around 1.7 TPC molecules per nanoparticle. According to the calibration curve of the fluorescence spectra of free peptide and the fluorescence of the peptide coupled to the nanoparticles in solution, we quantified ~ 3 peptides per nanoparticle.


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)

Absorption spectra, size and zeta potential of gadolinium-based hybrid silica nanoparticles. (A) Size distribution by volume of the hydrodynamic diameter (expressed in nm) of nanoparticles (NP-TPC-ATWLPPR or NP) in suspension at 20°C. (B) Zeta potential distribution (expressed in mV) of the nanoparticles (NP-TPC-ATWLPPR or NP) suspensions. (C) Absorption spectra of free photosensitizer TPC and suspension of NP-TPC-ATWLPPR nanoparticles in ethanol.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475218&req=5

Figure 1: Absorption spectra, size and zeta potential of gadolinium-based hybrid silica nanoparticles. (A) Size distribution by volume of the hydrodynamic diameter (expressed in nm) of nanoparticles (NP-TPC-ATWLPPR or NP) in suspension at 20°C. (B) Zeta potential distribution (expressed in mV) of the nanoparticles (NP-TPC-ATWLPPR or NP) suspensions. (C) Absorption spectra of free photosensitizer TPC and suspension of NP-TPC-ATWLPPR nanoparticles in ethanol.
Mentions: Size distribution and Zeta potential of the nanoparticles were presented in Fig. 1A and B, respectively, and values were summarized in Table 1. Hydrodynamic diameter was 4.6 and 3.3 nm for NP-TPC-ATLLPPR and NP, respectively. Hence, one can observe that peptide grafting on the surface of nanoparticles (~ 3 peptides per nanoparticle) and TPC encapsulating into the silica shell (~1.7 TPC molecules per nanoparticle) induce only slight increase in the hydrodynamic diameter (4.6 vs. 3.3 nm for NP-TPC-ATWLPPR and NP, respectively). The two nanoparticles batches were characterized by a single narrow peak with around 99.5% of the size distribution by volume (Fig. 1A). This indicates that the nanoparticles were monodisperse in water probably because of their derivatization by the DOTA polymers. Zeta potentials were also determined in ultrapure water to avoid the presence of counterions which could neutralize the charges on the nanoparticles. Positive charge of 12.9 ± 4.0 and 4.3 ± 3.5 mV was measured for NP-TPC-ATWLPPR and NP, respectively (Fig. 1B and Table 1). As suggested by our group 34, the higher positive charge of the peptide-conjugated nanoparticles (12.9±4.0 mV) may be brought by the surface-grafted peptide ATWLPPR (~ 3 peptides per nanoparticle). UV/Vis spectra of the NP-TPC-ATWLPPR nanoparticles showed that the nanoparticles displayed similar absorption features to free TPC, with the Soret-band and the respective Q-bands (Fig. 1C). No shift of the maximum absorption at Soret-band can be observed, suggesting that the photosensitizer was mainly in a monomeric form without aggregation inside the nanoparticles. This indicates that the photophysical properties of TPC molecules in the nanoparticles were well retained. According to the calibration curve of the UV/Vis absorption spectra of free TPC, the amount of grafted TPC within the nanoparticles NP-TPC-ATWLPPR was estimated around 1.7 TPC molecules per nanoparticle. According to the calibration curve of the fluorescence spectra of free peptide and the fluorescence of the peptide coupled to the nanoparticles in solution, we quantified ~ 3 peptides per nanoparticle.

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