Functional Single-Chain Polymer Nanoparticles: Targeting and Imaging Pancreatic Tumors in Vivo

Ana B. Benito; Miren K. Aiertza; Marco Marradi; Larraitz Gil-Iceta; Talia Shekhter Zahavi; Boguslaw Szczupak; María Jiménez-González; Torsten Reese; Eugenio Scanziani; Lorena Passoni; Michela Matteoli; Marcella De Maglie; Arie Orenstein; Mor Oron-Herman; Gennady Kostenich; Ludmila Buzhansky; Ehud Gazit; Hans Jurgen Grande; Vanessa Gómez-Vallejo; Jordi Llop; Iraida Loinaz

doi:10.1021/acs.biomac.6b00941

Functional Single-Chain Polymer Nanoparticles: Targeting and Imaging Pancreatic Tumors in Vivo

Ana B. Benito, Miren K. Aiertza, Marco Marradi, Larraitz Gil-Iceta, Talia Shekhter Zahavi, Boguslaw Szczupak, María Jiménez-González, Torsten Reese, Eugenio Scanziani, Lorena Passoni, Michela Matteoli, Marcella De Maglie, Arie Orenstein, Mor Oron-Herman, Gennady Kostenich, Ludmila Buzhansky, Ehud Gazit, Hans Jurgen Grande, Vanessa Gómez-Vallejo, Jordi LlopIraida Loinaz^*

^*Corresponding author for this work

Biotechnology

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

The development of tools for the early diagnosis of pancreatic adenocarcinoma is an urgent need in order to increase treatment success rate and reduce patient mortality. Here, we present a modular nanosystem platform integrating soft nanoparticles with a targeting peptide and an active imaging agent for diagnostics. Biocompatible single-chain polymer nanoparticles (SCPNs) based on poly(methacrylic acid) were prepared and functionalized with the somatostatin analogue PTR86 as the targeting moiety, since somatostatin receptors are overexpressed in pancreatic cancer. The gamma emitter ⁶⁷Ga was incorporated by chelation and allowed in vivo investigation of the pharmacokinetic properties of the nanoparticles using single photon emission computerized tomography (SPECT). The resulting engineered nanosystem was tested in a xenograph mouse model of human pancreatic adenocarcinoma. Imaging results demonstrate that accumulation of targeted SCPNs in the tumor is higher than that observed for nontargeted nanoparticles due to improved retention in this tissue.

Original language	English
Pages (from-to)	3213-3221
Number of pages	9
Journal	Biomacromolecules
Volume	17
Issue number	10
DOIs	https://doi.org/10.1021/acs.biomac.6b00941
State	Published - 10 Oct 2016

Funding

Funders	Funder number
Seventh Framework Programme	263307

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acs.biomac.6b00941

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Benito, A. B., Aiertza, M. K., Marradi, M., Gil-Iceta, L., Shekhter Zahavi, T., Szczupak, B., Jiménez-González, M., Reese, T., Scanziani, E., Passoni, L., Matteoli, M., De Maglie, M., Orenstein, A., Oron-Herman, M., Kostenich, G., Buzhansky, L., Gazit, E., Grande, H. J., Gómez-Vallejo, V., ... Loinaz, I. (2016). Functional Single-Chain Polymer Nanoparticles: Targeting and Imaging Pancreatic Tumors in Vivo. Biomacromolecules, 17(10), 3213-3221. https://doi.org/10.1021/acs.biomac.6b00941

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abstract = "The development of tools for the early diagnosis of pancreatic adenocarcinoma is an urgent need in order to increase treatment success rate and reduce patient mortality. Here, we present a modular nanosystem platform integrating soft nanoparticles with a targeting peptide and an active imaging agent for diagnostics. Biocompatible single-chain polymer nanoparticles (SCPNs) based on poly(methacrylic acid) were prepared and functionalized with the somatostatin analogue PTR86 as the targeting moiety, since somatostatin receptors are overexpressed in pancreatic cancer. The gamma emitter 67Ga was incorporated by chelation and allowed in vivo investigation of the pharmacokinetic properties of the nanoparticles using single photon emission computerized tomography (SPECT). The resulting engineered nanosystem was tested in a xenograph mouse model of human pancreatic adenocarcinoma. Imaging results demonstrate that accumulation of targeted SCPNs in the tumor is higher than that observed for nontargeted nanoparticles due to improved retention in this tissue.",

author = "Benito, {Ana B.} and Aiertza, {Miren K.} and Marco Marradi and Larraitz Gil-Iceta and {Shekhter Zahavi}, Talia and Boguslaw Szczupak and Mar{\'i}a Jim{\'e}nez-Gonz{\'a}lez and Torsten Reese and Eugenio Scanziani and Lorena Passoni and Michela Matteoli and {De Maglie}, Marcella and Arie Orenstein and Mor Oron-Herman and Gennady Kostenich and Ludmila Buzhansky and Ehud Gazit and Grande, {Hans Jurgen} and Vanessa G{\'o}mez-Vallejo and Jordi Llop and Iraida Loinaz",

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month = oct,

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doi = "10.1021/acs.biomac.6b00941",

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Benito, AB, Aiertza, MK, Marradi, M, Gil-Iceta, L, Shekhter Zahavi, T, Szczupak, B, Jiménez-González, M, Reese, T, Scanziani, E, Passoni, L, Matteoli, M, De Maglie, M, Orenstein, A, Oron-Herman, M, Kostenich, G, Buzhansky, L, Gazit, E, Grande, HJ, Gómez-Vallejo, V, Llop, J & Loinaz, I 2016, 'Functional Single-Chain Polymer Nanoparticles: Targeting and Imaging Pancreatic Tumors in Vivo', Biomacromolecules, vol. 17, no. 10, pp. 3213-3221. https://doi.org/10.1021/acs.biomac.6b00941

TY - JOUR

T1 - Functional Single-Chain Polymer Nanoparticles

T2 - Targeting and Imaging Pancreatic Tumors in Vivo

AU - Benito, Ana B.

AU - Aiertza, Miren K.

AU - Marradi, Marco

AU - Gil-Iceta, Larraitz

AU - Shekhter Zahavi, Talia

AU - Szczupak, Boguslaw

AU - Jiménez-González, María

AU - Reese, Torsten

AU - Scanziani, Eugenio

AU - Passoni, Lorena

AU - Matteoli, Michela

AU - De Maglie, Marcella

AU - Orenstein, Arie

AU - Oron-Herman, Mor

AU - Kostenich, Gennady

AU - Buzhansky, Ludmila

AU - Gazit, Ehud

AU - Grande, Hans Jurgen

AU - Gómez-Vallejo, Vanessa

AU - Llop, Jordi

AU - Loinaz, Iraida

PY - 2016/10/10

Y1 - 2016/10/10

N2 - The development of tools for the early diagnosis of pancreatic adenocarcinoma is an urgent need in order to increase treatment success rate and reduce patient mortality. Here, we present a modular nanosystem platform integrating soft nanoparticles with a targeting peptide and an active imaging agent for diagnostics. Biocompatible single-chain polymer nanoparticles (SCPNs) based on poly(methacrylic acid) were prepared and functionalized with the somatostatin analogue PTR86 as the targeting moiety, since somatostatin receptors are overexpressed in pancreatic cancer. The gamma emitter 67Ga was incorporated by chelation and allowed in vivo investigation of the pharmacokinetic properties of the nanoparticles using single photon emission computerized tomography (SPECT). The resulting engineered nanosystem was tested in a xenograph mouse model of human pancreatic adenocarcinoma. Imaging results demonstrate that accumulation of targeted SCPNs in the tumor is higher than that observed for nontargeted nanoparticles due to improved retention in this tissue.

AB - The development of tools for the early diagnosis of pancreatic adenocarcinoma is an urgent need in order to increase treatment success rate and reduce patient mortality. Here, we present a modular nanosystem platform integrating soft nanoparticles with a targeting peptide and an active imaging agent for diagnostics. Biocompatible single-chain polymer nanoparticles (SCPNs) based on poly(methacrylic acid) were prepared and functionalized with the somatostatin analogue PTR86 as the targeting moiety, since somatostatin receptors are overexpressed in pancreatic cancer. The gamma emitter 67Ga was incorporated by chelation and allowed in vivo investigation of the pharmacokinetic properties of the nanoparticles using single photon emission computerized tomography (SPECT). The resulting engineered nanosystem was tested in a xenograph mouse model of human pancreatic adenocarcinoma. Imaging results demonstrate that accumulation of targeted SCPNs in the tumor is higher than that observed for nontargeted nanoparticles due to improved retention in this tissue.

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AN - SCOPUS:84991080749

SN - 1525-7797

VL - 17

SP - 3213

EP - 3221

JO - Biomacromolecules

JF - Biomacromolecules

IS - 10

ER -

Functional Single-Chain Polymer Nanoparticles: Targeting and Imaging Pancreatic Tumors in Vivo

Abstract

Funding

UN SDGs

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