TY - JOUR
T1 - Intra-colonic administration of a polymer-bound NIRF probe for improved colorectal cancer detection during colonoscopy
AU - Kogan-Zviagin, Inga
AU - Shamay, Yosi
AU - Nissan, Aviram
AU - Sella-Tavor, Osnat
AU - Golan, Moran
AU - David, Ayelet
N1 - Funding Information: This study was supported by the Bio-Medical Photonics (BMP) Consortium within the Magnet program of the Israeli Ministry of Industry and Commerce, and by the Israeli National Nanotechnology Initiative for a Focal Technology Area (FTA) on Nanomedicines for Personalized Theranostics. We thank Prof. Ilana Ariel from the Department of Pathology, Perinatal Pathology Unit, Hadassah Mount Scopus in Jerusalem, for her assistance in the histological evaluation.
PY - 2014/10/28
Y1 - 2014/10/28
N2 - There is increasing interest in the use of nanoparticle imaging probes for cancer diagnosis. However, various biological barriers limit the efficient delivery of nanoparticles to tumors following parenteral administration. We have investigated the applicability of a water-soluble polymeric imaging probe for improving the detection of gastrointestinal (GI) tumors after intra-luminal (colonic) administration. N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers bearing either fluorescein-isothiocyanate (FITC) or near-infrared fluorescence (NIRF) dye (IR-783) were conjugated with EPPT1 peptide, derived from the CDR3 Vh region of a monoclonal antibody (ASM2) raised against human epithelial cancer cells, for targeting under-glycosylated mucin-1 (uMUC-1) expressed in neoplastic tissues. The targeted FITC-labeled copolymer, P-(EPPT1)-FITC, was investigated for its ability to bind human CRC cells and tissue specimens in vitro. The uMUC-1-targeted NIRF-labeled copolymer, P-(EPPT1)-IR783, was assessed for its ability to detect colonic lesions in vivo. P-(EPPT1)-FITC demonstrated superior binding to colorectal cancer (CRC) cells that over-express the uMUC-1 antigen and exhibited selectivity towards human CRC tissue specimens, as compared to adjacent normal tissues from the same patient. When applied intra-colonically, P-(EPPT1)-IR783 significantly accumulated in cancerous tissue, relative to the adjacent normal mucosa of HT29 and LS174T tumor-bearing mice, and demonstrated higher signal intensities in colonic tumors, as compared to the non-targeted P-(GG-OH)-IR783 probe (i.e., without EPPT1). We found that P-(GG-OH)-IR783 can also accumulate specifically at tumor sites. The cancer-specific uptake and retention of P-(GG-OH)-IR783 was not mediated by organic anion transporting peptides (OATPs). Our findings indicate that the polymer-bound NIRF probe can successfully detect solid tumors in the GI tract following intra-colonic administration, and could be used in conjunction with colonoscopic procedures to improve the sensitivity of colonoscopies for polyp detection.
AB - There is increasing interest in the use of nanoparticle imaging probes for cancer diagnosis. However, various biological barriers limit the efficient delivery of nanoparticles to tumors following parenteral administration. We have investigated the applicability of a water-soluble polymeric imaging probe for improving the detection of gastrointestinal (GI) tumors after intra-luminal (colonic) administration. N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers bearing either fluorescein-isothiocyanate (FITC) or near-infrared fluorescence (NIRF) dye (IR-783) were conjugated with EPPT1 peptide, derived from the CDR3 Vh region of a monoclonal antibody (ASM2) raised against human epithelial cancer cells, for targeting under-glycosylated mucin-1 (uMUC-1) expressed in neoplastic tissues. The targeted FITC-labeled copolymer, P-(EPPT1)-FITC, was investigated for its ability to bind human CRC cells and tissue specimens in vitro. The uMUC-1-targeted NIRF-labeled copolymer, P-(EPPT1)-IR783, was assessed for its ability to detect colonic lesions in vivo. P-(EPPT1)-FITC demonstrated superior binding to colorectal cancer (CRC) cells that over-express the uMUC-1 antigen and exhibited selectivity towards human CRC tissue specimens, as compared to adjacent normal tissues from the same patient. When applied intra-colonically, P-(EPPT1)-IR783 significantly accumulated in cancerous tissue, relative to the adjacent normal mucosa of HT29 and LS174T tumor-bearing mice, and demonstrated higher signal intensities in colonic tumors, as compared to the non-targeted P-(GG-OH)-IR783 probe (i.e., without EPPT1). We found that P-(GG-OH)-IR783 can also accumulate specifically at tumor sites. The cancer-specific uptake and retention of P-(GG-OH)-IR783 was not mediated by organic anion transporting peptides (OATPs). Our findings indicate that the polymer-bound NIRF probe can successfully detect solid tumors in the GI tract following intra-colonic administration, and could be used in conjunction with colonoscopic procedures to improve the sensitivity of colonoscopies for polyp detection.
KW - Colorectal cancer
KW - HPMA copolymer
KW - Imaging probe
KW - Intracolonic administration
KW - Near infrared fluorescence
UR - http://www.scopus.com/inward/record.url?scp=84905374869&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jconrel.2014.06.058
DO - https://doi.org/10.1016/j.jconrel.2014.06.058
M3 - مقالة
C2 - 25008468
SN - 0168-3659
VL - 192
SP - 182
EP - 191
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -
