Synthesis and biological investigations of a ZnPc-antiCEA bioconjugate for imaging of colorectal cancer

Abstract

Two zinc(II) phthalocyanines (ZnPcs) were conjugated with a monoclonal antibody (MAb) directed against carcinoembryonic antigen (CEA), using an in situ activated carboxylic acid on the ZnPcs. The bioconjugate with the highest ZnPc/MAb ratio of 3 was investigated in vitro for its ability to target and fluorescently label human colorectal HT-29 cells. The ZnPc-CEA MAb 2 was observed to efficiently target HT-29 cells, about 37 times more than unconjugated ZnPc. Furthermore, in the presence of a 4-fold excess of unlabelled anti-CEA antibody, the fluorescence signal of 2 was reduced by ~90% showing that the targeting is CEA-mediated. These studies further confirm the high specificity of Pc-antibody conjugates for antigens over-expressed on tumor cells and warrant further investigations of these immunoconjugates and their derivatives for imaging of colorectal cancer.

Porphyrinoid biohybrid materials as an emerging toolbox for biomedical light management

“…156 More recently, Vicente and co-workers synthesized two Zn(II)Pc-antiCEA conjugates through carbodiimide-mediated coupling reactions, targeting and labelling human colorectal HT-29 cells with higher efficiency compared to the free Zn(II)Pc. 157 Finally, CEA targeting with MAb was reported by Bouvet and co-workers, who synthesized an anti-CEA-IR700 conjugate that expressed an extensive tumour cell killing in pancreatic cancer in mice. 158 4.2.3.…”

Photodynamic diagnosis and photodynamic therapy of colorectal cancer in vitro and in vivo

“…In a study performed by Sehgal et al (2013), ZnPcS was conjugated to a monoclonal antibody directed against carcinoembryonic antigen (CEA) to enhance targeted PS uptake in CRC cells. 97 This bioconjugate was administered to in vitro cocultured HT-29 cells and normal colon epithelial cells, and the CRC cells noted a 37 times higher uptake, than when compared to unconjugated ZnPcS administration and normal colon epithelial cells reported no absorption. 97 These ndings suggest that CEA-mediated effective, as well as selective PS targeting in CRC cells only.…”

“…97 This bioconjugate was administered to in vitro cocultured HT-29 cells and normal colon epithelial cells, and the CRC cells noted a 37 times higher uptake, than when compared to unconjugated ZnPcS administration and normal colon epithelial cells reported no absorption. 97 These ndings suggest that CEA-mediated effective, as well as selective PS targeting in CRC cells only. 97 Additionally, when light excitation at 550 nm was applied to the co-culture, which received this bioconjugate, intense illumination was noted selectively within CRC cells only, with no phototoxicity being reported.…”

“…97 These ndings suggest that CEA-mediated effective, as well as selective PS targeting in CRC cells only. 97 Additionally, when light excitation at 550 nm was applied to the co-culture, which received this bioconjugate, intense illumination was noted selectively within CRC cells only, with no phototoxicity being reported. 97 Thus, this study demonstrated CRC cancer selective targeting of ZnPc-anti-CEA conjugate, suggesting it could be used as a PDD imaging agent for the uorescent surveillance of colon cancer foci-CEA conjugate as a lead imaging agent for uorescent surveillance of CRC foci.…”

Synthesis and investigation of phthalocyanine-biotin conjugates

“…In particular, isomerically pure Pcs bearing versatile functional groups can be used as templates to produce functionalized Pcs via, for example, esterification, substitution and acylation reactions [11][12][13][14][15][16][17][18][19]. The Pc templates can be conjugated to hydrophilic and cell-targeting moieties, yielding amphiphilic compounds with enhanced solubility, serum life, and specificity towards receptors overexpressed on cancer cells [11,14,[20][21][22]. This strategy is particularly useful when the required precursors bearing targeting moieties are not readily available or are unstable under cyclization conditions [23][24].…”