Engineering of near infrared fluorescent proteinoid-poly(L-lactic acid) particles for in vivo colon cancer detection

Journal of Nanobiotechnology

Shlomo Margel¹  Enav Corem-Salkmon¹  Igor Grinberg¹  Michal Kolitz-Domb¹ 

[1] Department of Chemistry, The Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900, Israel

关键词: Colon cancer;    Optical imaging;    NIR fluorescence;    Fluorescent nanoparticles;    Proteinoid nanoparticles;   

Others  :  1146384
DOI  :  10.1186/s12951-014-0030-z

 received in 2014-06-02, accepted in 2014-08-08,  发布年份 2014

【 摘 要 】

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.

Results and discussion

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.

【 授权许可】

   
2014 Kolitz-Domb et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Burt RW, Barthel JS, Dunn KB, David DS, Drelichman E, Ford JM, Giardiello FM, Gruber SB, Halverson AL, Hamilton SR: Colorectal cancer screening. J Natl Compr Canc Netw 2010, 8:8-61.
• [2]Nelson RS, Thorson AG: Colorectal cancer screening. Curr Oncol Rep 2009, 11:482-489.
• [3]Mandel JS, Church TR, Bond JH, Ederer F, Geisser MS, Mongin SJ, Snover DC, Schuman LM: The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Eng J Med 2000, 343:1603-1607.
• [4]Labianca R, Beretta GD, Mosconi S, Milesi L, Pessi MA: Colorectal cancer: screening. Ann Oncol 2005, 16:127-132.
• [5]Altınoğlu Eİ, Adair JH: Near infrared imaging with nanoparticles. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2010, 2:461-477.
• [6]Cohen S, Pellach M, Kam Y, Grinberg I, Corem-Salkmon E, Rubinstein A, Margel S: Synthesis and characterization of near IR fluorescent albumin nanoparticles for optical detection of colon cancer. Mat Sci Eng C 2012, 33:923-931.
• [7]Jiang S, Gnanasammandhan MK, Zhang Y: Optical imaging-guided cancer therapy with fluorescent nanoparticles. J R Soc Interface 2009, 7:3-18.
• [8]Santra S, Dutta D, Walter GA, Moudgil BM: Fluorescent nanoparticle probes for cancer imaging. Technol Cancer Res Treat 2005, 4:593-602.
• [9]Gluz E, Rudnick Glick S, Mizrahi DM, Chen R, Margel S: New biodegradable bisphosphonate vinylic monomers and near infrared fluorescent nanoparticles for biomedical applications. Polym Advan Technol 2014, 25:499-506.
• [10]Sharrna P, Brown S, Walter G, Santra S, Moudgil B: Nanoparticles for bioimaging. Adv Colloid Interfac 2006, 123:471-485.
• [11]Gluz E, Grinberg I, Corem-Salkmon E, Mizrahi D, Margel S: Engineering of new crosslinked near-infrared fluorescent polyethylene glycol bisphosphonate nanoparticles for bone targeting. J Polym Sci Pol Chem 2013, 51:4282-4291.
• [12]Metildi CA, Kaushal S, Luiken GA, Talamini MA, Hoffman RM, Bouvet M: Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient derived orthotopic xenograft (PDOX) nude mouse model. J Surg Oncol 2014, 109:451-458.
• [13]Saxena V, Sadoqi M, Shao J: Enhanced photo-stability, thermal-stability and aqueous-stability of indocyanine green in polymeric nanoparticulate systems. J Photoch Photobio B 2004, 74:29-38.
• [14]Quirk S: Triggered release of small molecules from proteinoid microspheres. J Biomed Mater Res, Part A 2009, 91A:391-399.
• [15]Quirk S: Triggered release from peptide-proteinoid microspheres. J Biomed Mater Res, Part A 2010, 92A:877-886.
• [16]Kumar ABM, Rao KP: Preparation and characterization of pH-sensitive proteinoid microspheres for the oral delivery of methotrexate. Biomaterials 1998, 19:725-732.
• [17]Fox SW, Waehneld T: Thermal synthesis of neutral and basic proteinoids. Biochim Biophys Acta 1968, 160:246-249.
• [18]Fox SW, Nakashima T, Przybylski A, Syren RM: The updated experimental proteinoid model. Int J Quantum Chem 1982, 22:195-204.
• [19]Fox SW, Harada K: The thermal copolymerization of amino acids common to protein. J Am Chem Soc 1959, 82:3745-3751.
• [20]Harada K, Fox SW: The thermal condensation of glutamic acid and glycine to linear peptides. J Am Chem Soc 1957, 80:2694-2697.
• [21]Kokufuta E, Sakai H, Harada K: Factors controlling the size of Proteinoid microspheres. BioSystems 1983, 16:175-181.
• [22]Auras R: Poly (lactic acid). In Encyclopedia Of Polymer Science and Technology. Wiley Interscience, Hoboken, NJ; 2010.
• [23]Tsuji H: Poly (lactic acid). In Bio-Based Plastics: Materials and Applications. Edited by Kabasci S. John Wiley & Sons, Chichester, UK; 2013:171-239.
• [24]Bahn PR, Pappelis A, Bozzola J: Protocell-like microspheres from thermal Polyaspartic acid. Orig Life Evol Biospheres 2006, 36:617-619.
• [25]Syren RM, Sanjur A, Fox SW: Proteinoid microspheres more stable in hot than in cold water. BioSystems 1985, 17:275-280.
• [26]Steiner S, Rosen R: Delivery systems for pharmacological agents encapsulated with proteinoids, vol. U.S. Patent No. 4,925,673. Washington, USA: ᅟ; 1990.
• [27]Haritoglou C, Freyer W, Priglinger SG, Kampik A: Light absorbing properties of indocyanine green (ICG) in solution and after adsorption to the retinal surface—an ex-vivo approach. Graef Arch Clin Exp 2006, 244:1196-1202.
• [28]Zweck J, Penzkofer A: Microstructure of indocyanine green J-aggregates in aqueous solution. Chem Phys 2001, 269:399-409.
• [29]Ma XH, Santiago N, Chen YS, Chaudhary K, Milstein SJ, Baughman RA: Stability study of drug-loaded proteinoid microsphere formulations during freeze-drying. J Drug Target 1994, 2:9-21.
• [30]Decker T, Lohmannmatthes ML: A quick and simple method for the quantitation of lactate-dehydrogenase release in measurements of cellular cyto-toxicity and Tumor Necrosis Factor (Tnf) activity. J Immunol Methods 1988, 115:61-69.
• [31]Yaseen MA, Yu J, Jung B, Wong MS, Anvari B: Biodistribution of encapsulated indocyanine green in healthy mice. Mol Pharm 2009, 6:1321-1332.
• [32]Mizrahi DM, Ziv-Polat O, Perlstein B, Gluz E, Margel S: Synthesis, fluorescence and biodistribution of a bone-targeted near-infrared conjugate. Eur J Med Chem 2011, 46:5175-5183.
• [33]Kaushal S, McElroy MK, Luiken GA, Talamini MA, Moossa A, Hoffman RM, Bouvet M: Fluorophore-conjugated anti-CEA antibody for the intraoperative imaging of pancreatic and colorectal cancer. J Gastrointest Surg 2008, 12:1938-1950.
• [34]Bae S, Ma K, Kim TH, Lee ES, Oh KT, Park ES, Lee KC, Youn YS: Doxorubicin-loaded human serum albumin nanoparticles surface-modified with TNF-related apoptosis-inducing ligand and transferrin for targeting multiple tumor types. Biomaterials 2012, 33:1536-1546.
• [35]Capdevila J, Elez E, Macarulla T, Ramos FJ, Ruiz-Echarri M, Tabernero J: Anti-epidermal growth factor receptor monoclonal antibodies in cancer treatment. Cancer Treat Rev 2009, 35:354-363.
• [36]Heiskanen J: Comparison of three methods for determining the particle density of soil with liquid pycnometers. Commun Soil Sci Plant Anal 1992, 23:841-846.
• [37]Epsztejn S, Glickstein H, Picard V, Slotki IN, Breuer W, Beaumont C, Cabantchik ZI: H-ferritin subunit overexpression in erythroid cells reduces the oxidative stress response and induces multidrug resistance properties. Blood 1999, 94:3593-3603.
• [38]Noiman T, Buzhor E, Metsuyanim S, Harari-Steinberg O, Morgenshtern C, Dekel B, Goldstein RS: A rapid in vivo assay system for analyzing the organogenetic capacity of human kidney cells. Organogenesis 2011, 7:140-144.