Synthesis and characterization of bioactive conjugated near-infrared fluorescent proteinoid-poly(L-lactic acid) hollow nanoparticles for optical detection of colon cancer.
Colon cancer is one of the major causes of death in the Western world. Early detection significantly improves long-term survival for patients with colon cancer. Near-infrared (NIR) fluorescent nanoparticles are promising candidates for use as contrast agents for tumor detection. Using NIR offers several advantages for bioimaging compared with fluorescence in the visible spectrum: lower autofluorescence of biological tissues and lower absorbance and, consequently, deeper penetration into biomatrices. The present study describes the preparation of new NIR fluorescent proteinoid-poly(L-lactic acid) (PLLA) nanoparticles. For this purpose, a P(EF-PLLA) random copolymer was prepared by thermal copolymerization of L-glutamic acid (E) with L-phenylalanine (F) and PLLA. Under suitable conditions, this proteinoid-PLLA copolymer can self-assemble to nanosized hollow particles of relatively narrow size distribution. This self-assembly process was used for encapsulation of the NIR dye indocyanine green. The encapsulation process increases significantly the photostability of the dye. These NIR fluorescent nanoparticles were found to be stable and nontoxic. Leakage of the NIR dye from these nanoparticles into phosphate-buffered saline containing 4% human serum albumin was not detected. Tumor-targeting ligands such as peanut agglutinin and anticarcinoembryonic antigen antibodies were covalently conjugated to the surface of the NIR fluorescent P(EF-PLLA) nanoparticles, thereby increasing the fluorescent signal of tumors with upregulated corresponding receptors. Specific colon tumor detection by the NIR fluorescent P(EF-PLLA) nanoparticles was demonstrated in a chicken embryo model. In future work, we plan to extend this study to a mouse model, as well as to encapsulate a cancer drug such as doxorubicin within these nanoparticles for therapeutic applications.
Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, Ramat Gan, Israel.
Michal
M
Kolitz-Domb
Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, Ramat Gan, Israel.
Enav
E
Corem-Salkmon
Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, Ramat Gan, Israel.
Igor
I
Grinberg
Institute of Nanotechnology and Advanced Materials, Department of Chemistry, Bar-Ilan University, Ramat Gan, Israel.
Shlomo
S
Margel
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects; D003110:Colonic Neoplasms / Q000737:chemistry / Q000175:diagnosis* / Q000188:drug therapy / Q000473:pathology; D004355:Drug Stability; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism; D010316:Particle Size; D010649:Phenylalanine / Q000737:chemistry; D011091:Polyesters; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D019265:Spectroscopy, Near-Infrared
D002272:Carcinoembryonic Antigen; D005456:Fluorescent Dyes; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; D018698:Glutamic Acid; C033616:poly(lactide); D010649:Phenylalanine
NIR fluorescence; fluorescent nanoparticles; hollow nanoparticles; proteinoid; self-assembly; thermal condensation