Ramona-Cosmina Adochite1, Anna Moshnikova1, Jovana Golijanin1, Oleg A Andreev1, Natallia V Katenka2, Yana K Reshetnyak3. 1. Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI, 02881, USA. 2. Department of Computer Sciences and Statistics, University of Rhode Island, 9 Greenhouse Road, Kingston, RI, 02881, USA. 3. Physics Department, University of Rhode Island, 2 Lippitt Road, Kingston, RI, 02881, USA. reshetnyak@uri.edu.
Abstract
PURPOSE: Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP(®) peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors. PROCEDURES: Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP(®) variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP(®) variants in multidimensional space of spectral parameters. RESULTS: The fluorescently labeled pHLIP(®) variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP(®) peptide. CONCLUSIONS: Different cargo molecules conjugated with pHLIP(®) peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP(®)-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions.
PURPOSE: Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP(®) peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors. PROCEDURES: Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP(®) variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP(®) variants in multidimensional space of spectral parameters. RESULTS: The fluorescently labeled pHLIP(®) variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP(®) peptide. CONCLUSIONS: Different cargo molecules conjugated with pHLIP(®) peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP(®)-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions.
Authors: Inna Serganova; Asif Rizwan; Xiaohui Ni; Sunitha B Thakur; Jelena Vider; James Russell; Ronald Blasberg; Jason A Koutcher Journal: Clin Cancer Res Date: 2011-08-15 Impact factor: 12.531
Authors: Bedrich L Eckhardt; Belinda S Parker; Ryan K van Laar; Christina M Restall; Anthony L Natoli; Michael D Tavaria; Kym L Stanley; Erica K Sloan; Jane M Moseley; Robin L Anderson Journal: Mol Cancer Res Date: 2005-01 Impact factor: 5.852
Authors: Jing Yang; Sendurai A Mani; Joana Liu Donaher; Sridhar Ramaswamy; Raphael A Itzykson; Christophe Come; Pierre Savagner; Inna Gitelman; Andrea Richardson; Robert A Weinberg Journal: Cell Date: 2004-06-25 Impact factor: 41.582
Authors: Amy L Vāvere; Gráinne B Biddlecombe; William M Spees; Joel R Garbow; Dayanjali Wijesinghe; Oleg A Andreev; Donald M Engelman; Yana K Reshetnyak; Jason S Lewis Journal: Cancer Res Date: 2009-05-05 Impact factor: 12.701
Authors: Stijn Keereweer; Jeroen D F Kerrebijn; Pieter B A A van Driel; Bangwen Xie; Eric L Kaijzel; Thomas J A Snoeks; Ivo Que; Merlijn Hutteman; Joost R van der Vorst; J Sven D Mieog; Alexander L Vahrmeijer; Cornelis J H van de Velde; Robert J Baatenburg de Jong; Clemens W G M Löwik Journal: Mol Imaging Biol Date: 2011-04 Impact factor: 3.488
Authors: Alexander A Svoronos; Raman Bahal; Mohan C Pereira; Francisco N Barrera; John C Deacon; Marcus Bosenberg; Daniel DiMaio; Peter M Glazer; Donald M Engelman Journal: Mol Pharm Date: 2020-01-13 Impact factor: 4.939
Authors: Linden C Wyatt; Anna Moshnikova; Troy Crawford; Donald M Engelman; Oleg A Andreev; Yana K Reshetnyak Journal: Proc Natl Acad Sci U S A Date: 2018-03-05 Impact factor: 11.205
Authors: Theyencheri Narayanan; Dhammika Weerakkody; Alexander G Karabadzhak; Michael Anderson; Oleg A Andreev; Yana K Reshetnyak Journal: J Phys Chem B Date: 2016-10-27 Impact factor: 2.991
Authors: Hannah Visca; Michael DuPont; Anna Moshnikova; Troy Crawford; Donald M Engelman; Oleg A Andreev; Yana K Reshetnyak Journal: Mol Imaging Biol Date: 2022-05-23 Impact factor: 3.484
Authors: Linden C Wyatt; Jason S Lewis; Oleg A Andreev; Yana K Reshetnyak; Donald M Engelman Journal: Trends Biotechnol Date: 2017-04-21 Impact factor: 19.536
Authors: Joseph Brito; Borivoj Golijanin; Ohad Kott; Anna Moshnikova; Catrina Mueller-Leonhard; Boris Gershman; Oleg A Andreev; Yana K Reshetnyak; Ali Amin; Dragan Golijanin Journal: Urology Date: 2019-01-16 Impact factor: 2.649