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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

Biodistribution of gadolinium-based hybrid silica nanoparticles with or without targeting peptide at 1h15 after intravenous injection (25 µmol of Gd/ ~ 250 g of body weight) in the caudal vein with NP-TPC-ATWLPPR (A) or NP (B). Gadolinium uptake was determined by ICP-MS analysis and expressed as percentage of the injected dose. Brain L: left brain hemisphere, Brain R: right brain hemisphere bearing xenografted tumor.
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Figure 7: Biodistribution of gadolinium-based hybrid silica nanoparticles with or without targeting peptide at 1h15 after intravenous injection (25 µmol of Gd/ ~ 250 g of body weight) in the caudal vein with NP-TPC-ATWLPPR (A) or NP (B). Gadolinium uptake was determined by ICP-MS analysis and expressed as percentage of the injected dose. Brain L: left brain hemisphere, Brain R: right brain hemisphere bearing xenografted tumor.

Mentions: Most interestingly however, distinct decrease rates of tumor MRI contrast kinetics from the maximum peak were observed according to nanoparticles type. Indeed, peptide-targeted nanoparticles showed slower time-dependent decrease (2.75-fold) of tumor MRI contrast as compared to non-targeted NP (-0.0072 vs. -0.0198 .min-1). Using the semi-logarithmic presentation of MRI contrast enhancement decrease kinetics (data not shown), half-life of peptide-targeted nanoparticles in the tumor tissue was estimated to be 2.75-fold than that of the non-targeted nanoparticles (T1/2 = 96.25 vs. 35.00 min). To evaluate in vivo biodistribution of the nanoparticles ~75 min post-intravenous injection, tumor-bearing rats were sacrificed at the end of MRI analysis and organs were subjected to gadolinium content quantification. Post-mortem ICP-MS analysis of the organs/tissues showed that whatever the nanoparticles groups gadolinium was detected in liver at low levels, but essentially present in kidneys and urine (Fig. 7), suggesting rapid clearance of the nanoparticles by the renal route.


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)

Biodistribution of gadolinium-based hybrid silica nanoparticles with or without targeting peptide at 1h15 after intravenous injection (25 µmol of Gd/ ~ 250 g of body weight) in the caudal vein with NP-TPC-ATWLPPR (A) or NP (B). Gadolinium uptake was determined by ICP-MS analysis and expressed as percentage of the injected dose. Brain L: left brain hemisphere, Brain R: right brain hemisphere bearing xenografted tumor.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3475218&req=5

Figure 7: Biodistribution of gadolinium-based hybrid silica nanoparticles with or without targeting peptide at 1h15 after intravenous injection (25 µmol of Gd/ ~ 250 g of body weight) in the caudal vein with NP-TPC-ATWLPPR (A) or NP (B). Gadolinium uptake was determined by ICP-MS analysis and expressed as percentage of the injected dose. Brain L: left brain hemisphere, Brain R: right brain hemisphere bearing xenografted tumor.
Mentions: Most interestingly however, distinct decrease rates of tumor MRI contrast kinetics from the maximum peak were observed according to nanoparticles type. Indeed, peptide-targeted nanoparticles showed slower time-dependent decrease (2.75-fold) of tumor MRI contrast as compared to non-targeted NP (-0.0072 vs. -0.0198 .min-1). Using the semi-logarithmic presentation of MRI contrast enhancement decrease kinetics (data not shown), half-life of peptide-targeted nanoparticles in the tumor tissue was estimated to be 2.75-fold than that of the non-targeted nanoparticles (T1/2 = 96.25 vs. 35.00 min). To evaluate in vivo biodistribution of the nanoparticles ~75 min post-intravenous injection, tumor-bearing rats were sacrificed at the end of MRI analysis and organs were subjected to gadolinium content quantification. Post-mortem ICP-MS analysis of the organs/tissues showed that whatever the nanoparticles groups gadolinium was detected in liver at low levels, but essentially present in kidneys and urine (Fig. 7), suggesting rapid clearance of the nanoparticles by the renal route.

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