title: Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection.
abstract: BACKGROUND
  The use of near-infrared (NIR) fluorescence imaging techniques has gained great interest for early detection of cancer owing to the negligible absorption and autofluorescence of water and other intrinsic biomolecules in this region. The main aim of the present study is to synthesize and characterize novel NIR fluorescent nanoparticles based on proteinoid and PLLA for early detection of colon tumors.
  
  
  METHODS
  The present study describes the synthesis of new proteinoid-PLLA copolymer and the preparation of NIR fluorescent nanoparticles for use in diagnostic detection of colon cancer. These fluorescent nanoparticles were prepared by a self-assembly process in the presence of the NIR dye indocyanine green (ICG), a FDA-approved NIR fluorescent dye. Anti-carcinoembryonic antigen antibody (anti-CEA), a specific tumor targeting ligand, was covalently conjugated to the P(EF-PLLA) nanoparticles through the surface carboxylate groups using the carbodiimide activation method.
  
  
  CONCLUSIONS
  The P(EF-PLLA) nanoparticles are stable in different conditions, no leakage of the encapsulated dye into PBS containing 4% HSA was detected. The encapsulation of the NIR fluorescent dye within the P(EF-PLLA) nanoparticles improves significantly the photostability of the dye. The fluorescent nanoparticles are non-toxic, and the biodistribution study in a mouse model showed they evacuate from the body over 24 h. Specific colon tumor detection in a chicken embryo model and a mouse model was demonstrated for anti-CEA-conjugated NIR fluorescent P(EF-PLLA) nanoparticles.
  
  
  CONCLUSIONS
  The results of this study suggest a significant advantage of NIR fluorescence imaging using NIR fluorescent P(EF-PLLA) nanoparticles over colonoscopy. In future work we plan to broaden this study by encapsulating cancer drugs such as paclitaxel and/or doxorubicin, within these biodegradable NIR fluorescent P(EF-PLLA) nanoparticles, for both detection and therapy of colon cancer.
authors.forename: Michal
authors.initials: M
authors.lastname: Kolitz-Domb
authors.forename: Igor
authors.initials: I
authors.lastname: Grinberg
authors.forename: Enav
authors.initials: E
authors.lastname: Corem-Salkmon
authors.forename: Shlomo
authors.initials: S
authors.lastname: Margel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002642:Chick Embryo; D003110:Colonic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D061848:Optical Imaging / Q000379:methods*; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D002272:Carcinoembryonic Antigen; D005456:Fluorescent Dyes; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D007208:Indocyanine Green
references.citation: Biomaterials. 2012 Feb;33(5):1536-46
references.pmid: 22118776
references.citation: Cancer Treat Rev. 2009 Jun;35(4):354-63
references.pmid: 19269105
references.citation: Ann Oncol. 2005;16 Suppl 2:ii127-32
references.pmid: 15958442
references.citation: Technol Cancer Res Treat. 2005 Dec;4(6):593-602
references.pmid: 16292879
references.citation: J Photochem Photobiol B. 2004 Mar 19;74(1):29-38
references.pmid: 15043844
references.citation: Orig Life Evol Biosph. 2006 Dec;36(5-6):617-9
references.pmid: 17120121
references.citation: N Engl J Med. 2000 Nov 30;343(22):1603-7
references.pmid: 11096167
references.citation: Curr Oncol Rep. 2009 Nov;11(6):482-9
references.pmid: 19840526
references.citation: Mater Sci Eng C Mater Biol Appl. 2013 Mar 1;33(2):923-31
references.pmid: 25427507
references.citation: J Gastrointest Surg. 2008 Nov;12(11):1938-50
references.pmid: 18665430
references.citation: J R Soc Interface. 2010 Jan 6;7(42):3-18
references.pmid: 19759055
references.citation: Biochim Biophys Acta. 1968 Jun 26;160(2):246-9
references.pmid: 5658125
references.citation: Biomaterials. 1998 Apr-May;19(7-9):725-32
references.pmid: 9663746
references.citation: Organogenesis. 2011 Apr-Jun;7(2):140-4
references.pmid: 21613816
references.citation: J Surg Oncol. 2014 Apr;109(5):451-8
references.pmid: 24249594
references.citation: Mol Pharm. 2009 Sep-Oct;6(5):1321-32
references.pmid: 19799463
references.citation: Adv Colloid Interface Sci. 2006 Nov 16;123-126:471-85
references.pmid: 16890182
references.citation: J Immunol Methods. 1988 Nov 25;115(1):61-9
references.pmid: 3192948
references.citation: J Biomed Mater Res A. 2010 Mar 1;92(3):877-86
references.pmid: 19280626
references.citation: J Biomed Mater Res A. 2009 Nov;91(2):391-9
references.pmid: 18980224
references.citation: Eur J Med Chem. 2011 Oct;46(10):5175-83
references.pmid: 21903304
references.citation: J Drug Target. 1994;2(1):9-21
references.pmid: 8069587
references.citation: Biosystems. 1985;17(4):275-80
references.pmid: 4052589
references.citation: Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 Sep-Oct;2(5):461-77
references.pmid: 20135691
references.citation: Blood. 1999 Nov 15;94(10):3593-603
references.pmid: 10552971
references.citation: Biosystems. 1983-1984;16(3-4):175-81
references.pmid: 6673778
references.citation: J Natl Compr Canc Netw. 2010 Jan;8(1):8-61
references.pmid: 20064289
references.citation: Graefes Arch Clin Exp Ophthalmol. 2006 Sep;244(9):1196-202
references.pmid: 16518658