Functional Single-Chain Polymer Nanoparticles: Targeting and Imaging Pancreatic Tumors in Vivo.
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 emitter67Ga 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.
IK4-CIDETEC, P° Miramón 196, 20014 Donostia-San Sebastián, Spain.
Ana B
AB
Benito
IK4-CIDETEC, P° Miramón 196, 20014 Donostia-San Sebastián, Spain.
Miren K
MK
Aiertza
IK4-CIDETEC, P° Miramón 196, 20014 Donostia-San Sebastián, Spain.
Marco
M
Marradi
CIC biomaGUNE, P° Miramón 182, 20014 Donostia-San Sebastián, Spain.
Larraitz
L
Gil-Iceta
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University , Ramat Aviv, Tel Aviv 69978, Israel.
Talia
T
Shekhter Zahavi
CIC biomaGUNE, P° Miramón 182, 20014 Donostia-San Sebastián, Spain.
Boguslaw
B
Szczupak
CIC biomaGUNE, P° Miramón 182, 20014 Donostia-San Sebastián, Spain.
María
M
Jiménez-González
CIC biomaGUNE, P° Miramón 182, 20014 Donostia-San Sebastián, Spain.
Torsten
T
Reese
Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.|Dipartimento di Medicina Veterinaria, Università degli Studi di Milano , Via Celoria 10, 20133, Milan, Italy.
Eugenio
E
Scanziani
Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
Lorena
L
Passoni
Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.
Michela
M
Matteoli
Fondazione Filarete, Viale Ortles 22/4, 20139 Milano, Italy.|Dipartimento di Medicina Veterinaria, Università degli Studi di Milano , Via Celoria 10, 20133, Milan, Italy.
Marcella
M
De Maglie
The Advanced Technologies Center, Sheba Medical Center , Tel Hashomer 52621, Israel.
Arie
A
Orenstein
The Advanced Technologies Center, Sheba Medical Center , Tel Hashomer 52621, Israel.
Mor
M
Oron-Herman
The Advanced Technologies Center, Sheba Medical Center , Tel Hashomer 52621, Israel.
Gennady
G
Kostenich
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University , Ramat Aviv, Tel Aviv 69978, Israel.
Ludmila
L
Buzhansky
Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University , Ramat Aviv, Tel Aviv 69978, Israel.
Ehud
E
Gazit
IK4-CIDETEC, P° Miramón 196, 20014 Donostia-San Sebastián, Spain.
Hans-Jurgen
HJ
Grande
CIC biomaGUNE, P° Miramón 182, 20014 Donostia-San Sebastián, Spain.
Vanessa
V
Gómez-Vallejo
CIC biomaGUNE, P° Miramón 182, 20014 Donostia-San Sebastián, Spain.
Jordi
J
Llop
IK4-CIDETEC, P° Miramón 196, 20014 Donostia-San Sebastián, Spain.
Iraida
I
Loinaz
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000818:Animals; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011108:Polymers / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000737:chemistry; D013004:Somatostatin / Q000096:biosynthesis* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D011108:Polymers; D011109:Polymethacrylic Acids; C030613:polymethacrylic acid; D013004:Somatostatin